Evidence Repository - Clinical Genome Resources

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_001754.4(RUNX1):c.613+7G>A

CA637745016

532680 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 78ef5404-eace-4acf-bdb3-8b6dc83c3391

Approved on: 2022-07-07

Published on: 2022-07-07

HGVS expressions

NM_001754.4:c.613+7G>A

NM_001754.4(RUNX1):c.613+7G>A

NC_000021.9:g.34859467C>T

CM000683.2:g.34859467C>T

NC_000021.8:g.36231764C>T

CM000683.1:g.36231764C>T

NC_000021.7:g.35153634C>T

NG_011402.2:g.1130245G>A

ENST00000675419.1:c.613+7G>A

ENST00000300305.7:c.613+7G>A

ENST00000344691.8:c.532+7G>A

ENST00000358356.9:c.532+7G>A

ENST00000399237.6:c.577+7G>A

ENST00000399240.5:c.532+7G>A

ENST00000437180.5:c.613+7G>A

ENST00000467577.1:n.105+7G>A

ENST00000482318.5:c.*203+7G>A

NM_001001890.2:c.532+7G>A

NM_001122607.1:c.532+7G>A

NM_001001890.3:c.532+7G>A

NM_001122607.2:c.532+7G>A

NM_001754.5:c.613+7G>A

NM_001754.5(RUNX1):c.613+7G>A

Likely Benign

BP7 BP4

BS2 PVS1 BS3 BS4 BS1 BP5 BP2 BP3 BP1 PS3 PS2 PS4 PS1 PP1 PP4 PP3 PP2 BA1 PM6 PM2 PM3 PM1 PM4 PM5

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Myeloid Malignancy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

This c.613+7G>A intronic variant is located at a weakly conserved nucleotide per an evolutionary conservation prediction algorithm (PhyloP score = 1.15676 in GRCh38); it is not predicted to have any splicing impact per SpliceAI (Δ scores ≤ 0.20) (BP7+BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4 and BP7.

BP7

Intronic variant located at a weakly conserved nucleotide (PhyloP = 1.15676 in GRCh38), although the variant is not the reference nucleotide in one primate and/or 3 mammals. SpliceAI does not show a splicing impact.

BP4

This intronic variant is not predicted by SpliceAI, MES, and SSF-like to have an impact on the canonical splice site or create putative cryptic splice sites (no significant score changes including SpliceAI Δ scores ≤ 0.20).

BS2

Not applicable.

PVS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS3

No reports of the variant in the literature (ClinVar, HGMD, LOVD, COSMIC).

BS4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS1

gnomAD v2: ALL:0.00080% (2/251474 alleles) - EAS:0.011% (2/18394 alleles, no homozygotes) gnomAD v3: Absent (>20x coverage)

BP5

Not applicable

BP2

No homozygotes reported in gnomAD v2 or v3. No case reports.

BP3

Not applicable

BP1

Not applicable

PS3

No reports of the variant in the literature (ClinVar, HGMD, LOVD, COSMIC).

PS2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS4

No reports of the variant in the literature (ClinVar, HGMD, LOVD, COSMIC).

PS1

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

PP4

Not applicable

PP3

This intronic variant is not predicted by SpliceAI, MES, and SSF-like to have an impact on the canonical splice site or create putative cryptic splice sites.

PP2

Not applicable

BA1

gnomAD v2: ALL:0.00080% (2/251474 alleles) - EAS:0.011% (2/18394 alleles, no homozygotes) gnomAD v3: Absent (>20x coverage)

PM6

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2

gnomAD v2: ALL:0.00080% (2/251474 alleles) - EAS:0.011% (2/18394 alleles, no homozygotes) gnomAD v3: Absent (>20x coverage)

PM3

Not applicable

PM1

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

PM5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

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