Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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  • See Evidence submitted by expert panel for details.

Variant: NM_000314.6(PTEN):c.210-7_210-3del5

CA059460

142397 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 48b4a5b9-e1c5-421f-b71f-26b8643652bc
Approved on: 2019-03-05
Published on: 2019-07-23

HGVS expressions

NM_000314.6:c.210-7_210-3delCTTTT
NM_000314.6:c.210-7_210-3del
NM_000314.6(PTEN):c.210-7_210-3del5
NC_000010.11:g.87931039_87931043del
CM000672.2:g.87931039_87931043del
NC_000010.10:g.89690796_89690800del
CM000672.1:g.89690796_89690800del
NC_000010.9:g.89680776_89680780del
NG_007466.2:g.72601_72605del
NM_000314.5:c.210-7_210-3del
NM_001304717.2:c.729-7_729-3del
NM_001304718.1:c.-541-7_-541-3del
NM_000314.7:c.210-7_210-3del
NM_001304717.5:c.729-7_729-3del
NM_001304718.2:c.-541-7_-541-3del
ENST00000371953.7:c.210-7_210-3del
ENST00000498703.1:n.36-7_36-3del
ENST00000610634.1:c.108-7_108-3del

Benign

Met criteria codes 2
BS1 BS3
Not Met criteria codes 20
PVS1 BA1 BP7 BP5 BP4 BP2 BS4 BS2 PP2 PP3 PP1 PM2 PM6 PM5 PM4 PM1 PS1 PS4 PS2 PS3

Evidence Links 13

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.210-7_210-3delCTTTT (IVS3-7_IVS3-3delCTTTT) meets criteria to be classified as benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). BS1: Allele frequency of 0.00136 (0.14%, 14/10,306 alleles) in the Ashkenazi Jewish subpopulation of the gnomAD cohort. (PMID 27535533) BS3: Intronic OR synonymous variant with RNA, mini-gene, or other splicing assay demonstrating no splicing impact. (PMID 28677221)
Met criteria codes
BS1
Variant present at allele frequency of 0.14% (14/10,306 alleles) in Ashkenazi Jewish subpop in gnomAD
BS3
Chen 2017
No splicing effect by mRNA testing (pt lymphoblast-derived cell lines were used). PubMed:28677221
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
1 GDx internal case HOM and unaffected but no parental testing performed (pt >80 yrs old). If additional unaffected HOM identified, could apply BS2 or BS2_supporting if BS1 also applies.
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
If BS1 met, PS4/PP4 cannot apply
Author overlap and cohort overlap with PMIDs 25186627, 26976419. PubMed:27443514
Reported in a pt having clinical PTEN testing, no phenotype info given. PubMed:21659347
Variant listed as identified in this study in Supplementary Table 4. No additional patient specific information reported. PubMed:25669429
seen in 6 year old monozygotic twins with Juvenile Polyposis syndrome (JPS) (5 ham polyps each), but also in their clinically unaffected father. twins had nml OFC and development. dad no skin lesions, polyps, thyroid issues. RNA studies in dad found two abnormal transcripts (one shorter, one longer) compared to WT but no details provided re: whether sizes were close to that expected if variant should induce abnormal splicing. Very importantly, neither SMAD4 nor BMPR1A were analyzed in the patients. PubMed:11156385
Variant present in 11 pts from CCF PTEN study (probands or relatives). 3 with CC score and/or box checked for "negative for phenotypes of interest". One with CC score = 42 (macrocephaly, BrCA, benign thyroid, hamartomas, GU tumor, AK, papillomas) but given BS1 applies, can't apply PS4/PP4 criteria anyways. PubMed:28677221
Identified in a male with ocular, melanoma, prostate, and bladder cancers. Positive family history noted, with no additional information. PubMed:29360161
41-year-old female with ascending colon cancer. Could be possible cohort overlap with PMIDs 25186627, 26976419, 27443514. PubMed:27978560
1 patient with variant in a cohort of endometrial cancer patients. PubMed:15589575
Identified in at least 1 patient with breast cancer who had testing using a NGS 25-gene panel. PubMed:25186627
Listed one of the pts also reported in Chen 2017 (60yo F with BrCA, macrocephaly, benign thyroid disease, lipomas); pt noted to have high plasma and urine succinate levels. No SDHx variants. PubMed:22261759
Author overlap and cohort overlap with PMID 25186627. PubMed:26976419
observed in 2/80 individuals undergoing whole genome sequencing. Ages were not reported. Also status of participants was noted as "presumably healthy", enrolled in IRB study for hereditary cancer susceptibility. PubMed:22995991
Identified in patient 3U as IVS3-3~7delCTTTT, diagnosed at 63y with pancolonic hyperplastic polyps and tubular adenomas, macrocephaly, non-small cell lung cancer (62y) and invasive ductal carcinoma (63y). CC score estimate = 13. PubMed:16287957
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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