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_030662.3(MAP2K2):c.919+4C>T

CA9090795

40834 (ClinVar)

Gene: MAP2K2

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 246061da-c54d-4473-bf35-633ebf160104

Approved on: 2019-07-25

Published on: 2019-12-03

HGVS expressions

NM_030662.3:c.919+4C>T

NM_030662.3(MAP2K2):c.919+4C>T

NC_000019.10:g.4099197G>A

CM000681.2:g.4099197G>A

NC_000019.9:g.4099195G>A

CM000681.1:g.4099195G>A

NC_000019.8:g.4050195G>A

NG_007996.1:g.29932C>T

ENST00000262948.9:c.919+4C>T

ENST00000394867.8:c.628+4C>T

ENST00000593364.5:n.870C>T

ENST00000595715.1:n.734+4C>T

ENST00000597263.5:n.169+1822C>T

ENST00000599021.1:n.29+1822C>T

ENST00000600584.5:n.1479+4C>T

ENST00000601786.5:n.1220+4C>T

Likely Benign

BP7 BP4

BS2 BS1

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The variant c.919+4C>T is an intronic variant at a nucleotide that is not highly conserved and is not predicted to impact splicing (BP7). Also, computational prediction tools and conservation analysis suggests that the variant does not impact the protein (BP4). In summary, the clinical significance of the c.919+4C>T variant is likely benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BP4, BP7.

BP7

Intronic variant not predicted to impact splicing and not evolutionarily conserved.

BP4

No predicted splice impact, not conserved and present in 7 other species including several reptiles.

BS2

Variant identified in a prenatal chorionic villus specimen obtained from a male fetus undergoing testing for Noonan Syndrome and Related Conditions on an NGS panel of 9 genes. The clinical indication was ‘Abnormal fetal ultrasound findings’ and no other pathogenic or VUS findings were reported. The final result interpretation was 'Negative' and not supporting an increased risk of Noonan syndrome or related conditions. Additionally, no numerical abnormalities for chromosomes 13, 18, 21, X and Y were identified. Mutated in colorectal cancer (MCC) analysis was performed and no contamination was detected. Chromosomal microarray results were positive for a heterozygous 79 KB interstitial deletion of 15q24.2->24.3 that was reported to span one gene (ETFA) associated with autosomal recessive glutaric academia IIA (Integrated Genetics internal data). Cannot be counted due to age requirement.

BS1

Present in 8/111196 (.0035% MAF 95% CI) non-Finnish European alleles in gnomAD

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