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]
Link to SEPIO compliant JSON-LD document

Variant: NM_177438.2(DICER1):c.4910C>T (p.Ser1637Leu)

CA7330772

242127 (ClinVar)

Gene: DICER1
Condition: dicer1 syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: c9daa85f-dbd7-4827-94cc-e41a19904f0c
Approved on: 2022-05-18
Published on: 2022-07-08

HGVS expressions

NM_177438.2:c.4910C>T
NM_177438.2(DICER1):c.4910C>T (p.Ser1637Leu)
NC_000014.9:g.95096010G>A
CM000676.2:g.95096010G>A
NC_000014.8:g.95562347G>A
CM000676.1:g.95562347G>A
NC_000014.7:g.94632100G>A
NG_016311.1:g.66413C>T
ENST00000343455.8:c.4910C>T
ENST00000393063.6:c.4910C>T
ENST00000526495.6:c.4910C>T
ENST00000532939.3:c.4910C>T
ENST00000556045.6:c.4910C>T
ENST00000675540.1:n.2655C>T
ENST00000675995.1:c.*3226C>T
ENST00000343455.7:c.4910C>T
ENST00000393063.5:c.4910C>T
ENST00000526495.5:c.4910C>T
ENST00000527414.5:c.4910C>T
ENST00000532939.2:n.945C>T
ENST00000541352.5:c.4910C>T
ENST00000556045.5:c.1604C>T
NM_001195573.1:c.4910C>T
NM_001271282.2:c.4910C>T
NM_001291628.1:c.4910C>T
NM_030621.4:c.4910C>T
NM_001271282.3:c.4910C>T
NM_001291628.2:c.4910C>T
NM_177438.3:c.4910C>T
NM_001395677.1:c.4910C>T
NM_001395678.1:c.4910C>T
NM_001395679.1:c.4910C>T
NM_001395680.1:c.4910C>T
NM_001395682.1:c.4910C>T
NM_001395683.1:c.4910C>T
NM_001395684.1:c.4910C>T
NM_001395685.1:c.4910C>T
NM_001395686.1:c.4628C>T
NM_001395687.1:c.4505C>T
NM_001395688.1:c.4505C>T
NM_001395689.1:c.4505C>T
NM_001395690.1:c.4505C>T
NM_001395691.1:c.4343C>T
NM_001395692.1:c.4910C>T
NM_001395693.1:c.4910C>T
NM_001395694.1:c.4910C>T
NM_001395695.1:c.4910C>T
NM_001395696.1:c.4505C>T
NM_001395697.1:c.3227C>T
NR_172715.1:n.5328C>T
NR_172716.1:n.5512C>T
NR_172717.1:n.5422C>T
NR_172718.1:n.5345C>T
NR_172719.1:n.5178C>T
NR_172720.1:n.5255C>T
NM_177438.3(DICER1):c.4910C>T (p.Ser1637Leu)

Benign

Met criteria codes 3
BS1 BS2 BP4
Not Met criteria codes 11
BA1 BS4 BS3 PS2 PS3 PS1 PP4 PP1 PM6 PM2 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen DICER1 and miRNA-Processing Gene Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for DICER1 Version 1

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
DICER1 and miRNA-Processing Gene VCEP
NM_177438.2(DICER1):c.4910C>T variant in DICER1 is a missense variant predicted to cause substitution of serine by leucine at amino acid 1637 (p.Ser1637Leu). The highest population minor allele frequency in gnomAD v2.1.1 non-cancer is 0.0026 (61/23614 alleles) in African/African-American population, which is higher than the ClinGen DICER1 VCEP threshold (>0.0003) for BS1, and therefore meets this criterion (BS1). This variant has been seen in 40 or more unrelated females without tumors through age 50 in at least one testing laboratory (BS2; Internal lab contributors/GTRs: 61756, 500031). The computational predictor REVEL gives a score of 0.065, which is below the threshold of 0.5, and the splice site predictors MaxEntScan and SpliceAI indicate that the variant has no impact on splicing, evidence that does not predict a damaging effect on DICER1 function (BP4). In summary, this variant meets the criteria to be classified as Benign for DICER1 syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BS1, BS2, BP4 (Bayesian Points: -9; VCEP specifications version 1; 02/11/2022).
Met criteria codes
BS1
0.26% (61/23614) African population (Gnomad 2.1.1 non-cancer); Latino 0.06% (12/35108)
BS2
>40 individuals with tumor-free through age 50
BP4
REVEL score 0.065 (< 0.50) and no splicing impact
Not Met criteria codes
BA1
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
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
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
PM6
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
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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