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_001754.4(RUNX1):c.1098_1103dupCGGCAT (p.Gly367_Met368insIleGly)

239040 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 06359166-e7e4-4c6e-8e13-8246247788c2
Approved on: 2021-02-20
Published on: 2023-11-13

HGVS expressions

NM_001754.4:c.1098_1103dupCGGCAT
NM_001754.4:c.1098_1103dup6
NM_001754.4(RUNX1):c.1098_1103dupCGGCAT (p.Gly367_Met368insIleGly)
NM_001754.5(RUNX1):c.1092CGGCAT[3] (p.364IG[3])

Likely Benign

Met criteria codes 1
BS1
Not Met criteria codes 25
PM2 PM6 PM1 PM4 PM5 PM3 BA1 PVS1 BS2 BS3 BS4 PS3 PS1 PS2 PS4 BP3 BP4 BP1 BP2 BP7 BP5 PP3 PP2 PP4 PP1

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
The NM_001754.5(RUNX1):c.1098_1103dup (p.Ile366_Gly367dup) variant has a highest MAF 0.0001618 (11 out of 67990 alleles) in European (non-Finnish) subpopulation of gnomAD v3.1 (BS1). In summary, the clinical significance of this variant is Likely Benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1.
Met criteria codes
BS1
This variant has a MAF 0.0001618 (11 out of 67990 alleles) in European (non-Finnish) subpopulation of gnomAD v3.1.
Not Met criteria codes
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
Both probands carrying this variant were reported to have no family history; however, no evidence showed parental studies were performed. In addition, limited paternal information was reported in one family.
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
In frame insertion not in RUNT domain.
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
PM3 is not applicable, because the RUNX1 associated disorder is under dominant inheritance.
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
Seen in at least 31 individuals unrelated or unaffected from internal laboratory (SCV000287177.4). None of these individuals have signs of myelodysplasia.
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No evidence
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
PS2
No evidence
PS4
The variant has to be either absent from gnomAD or only present once to apply PS4 codes. Although this variant was reported twice in probands meeting RUNX1 phenotypic criteria (PMID: 27210295, PMID: 28659335), it presents 17 times in gnomAD v2.1.1 and 16 times in gnomAD v.3.1.
This variant has been reported in a 13-year-old girl with lifetime mild thrombocytopenia and her bone marrow biopsy sample demonstrated abnormal megakaryocytes without morphologic criteria for MDS when test was performed PubMed:27210295
The variant was reported in a 14-year-old female with familial platelet disorder with hematological malignancy. PubMed:28659335
BP3
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
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
Not observed either in trans or in cis with a pathogenic variant
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
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
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 evidence
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