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]

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Variant: NM_001754.4(RUNX1):c.552G>T (p.Pro184=)

CA10014477

463997 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5a0293b1-7a32-4d97-af20-bdad5efd6bce

Approved on: 2020-08-24

Published on: 2021-01-12

HGVS expressions

NM_001754.4:c.552G>T

NM_001754.4(RUNX1):c.552G>T (p.Pro184=)

NM_001001890.2:c.471G>T

NM_001122607.1:c.471G>T

NM_001001890.3:c.471G>T

NM_001122607.2:c.471G>T

NM_001754.5:c.552G>T

ENST00000300305.7:c.552G>T

ENST00000344691.8:c.471G>T

ENST00000358356.9:c.471G>T

ENST00000399237.6:c.516G>T

ENST00000399240.5:c.471G>T

ENST00000437180.5:c.552G>T

ENST00000467577.1:n.44G>T

ENST00000482318.5:c.*142G>T

NC_000021.9:g.34859535C>A

CM000683.2:g.34859535C>A

NC_000021.8:g.36231832C>A

CM000683.1:g.36231832C>A

NC_000021.7:g.35153702C>A

NG_011402.2:g.1130177G>T

Benign

BP7 BP4 BA1

BS1 BS3 BS4 PVS1 BP2 PS1 PS3 PS4 PP3 PP1 PM5 PM4 PM1 PM2 PM6

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

The c.552G>T variant predicts a synonymous change, Pro184= and has an MAF of 0.001654 (0.17%, 33/19954 alleles) in the East Asian subpopulation of the gnomAD v2.1.1 cohort and is ≥ 0.0015 (0.15%) (BA1). This synonymous variant is predicted by SSF and MES to lead to either an increase in the canonical splice site score or a decrease of the canonical splice site score by no more than 10% and no putative cryptic splice sites are created (BP4). In addition, evolutionary conservation prediction algorithms predict the site as not being highly conserved (PhyloP score -8.975 < 0.1) (BP7). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP4, BP7.

BP7

No splicing impact predicted by SSF and MES. No concordance between the predictors on creation of cryptic sites. Also, SpliceAI predicts no splicing impact due to the variant (score: 0.00). UCSC gives a PhyloP score of -8.975 (<0.01 = not conserved).

BP4

No splicing impact predicted by SSF and MES. No concordance between the predictors on creation of cryptic sites. Also, SpliceAI predicts no splicing impact due to the variant (score: 0.00).

BA1

The Pro184= variant is reported at the highest MAF in the East Asian population in gnomAD v2.1.1, at a frequency of 0.001654 (33/19954 alleles), with 0 homozygotes.

BS1

Variant meets BA1

BS3

N/A

BS4

N/A

PVS1

N/A

BP2

N/A

PS1

N/A

PS3

N/A

PS4

N/A

PP3

N/A

PP1

N/A

PM5

N/A

PM4

N/A

PM1

N/A

PM2

Variant meets BA1

PM6

N/A

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