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.*8C>T

CA137903

46223 (ClinVar)

Gene: MAP2K2

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ccf6cba7-1870-484b-aeae-e6fcd0cace13

Approved on: 2024-09-17

Published on: 2024-10-02

HGVS expressions

NM_030662.3:c.*8C>T

NM_030662.3(MAP2K2):c.*8C>T

NC_000019.10:g.4090590G>A

CM000681.2:g.4090590G>A

NC_000019.9:g.4090588G>A

CM000681.1:g.4090588G>A

NC_000019.8:g.4041588G>A

NG_007996.1:g.38539C>T

ENST00000394867.9:n.1650C>T

ENST00000688002.1:n.3362C>T

ENST00000688751.1:n.347C>T

ENST00000689792.1:n.1115C>T

ENST00000262948.10:c.*8C>T

ENST00000262948.9:c.*8C>T

ENST00000394867.8:c.*8C>T

ENST00000597263.5:n.396C>T

ENST00000600584.5:n.2660C>T

ENST00000601786.5:n.1512C>T

NM_030662.4:c.*8C>T

Likely Benign

BP5 BP7

PS4 PM2 BA1 BS1

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specification: ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MAP2K2 Version 2.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.*8C>T variant in the MAP2K2 gene is located in the untranslated mRNA region downstream of the termination codon. The filtering allele frequency in gnomAD v4.1.0 is 0.01257%(172/1145270 alleles) in non-Finnish European population (PM2_Supporting/BS1/BA1 are not met). This variant is at a nucleotide that is not highly conserved and is not predicted to impact splicing (BP7). The c.*8C>T variant has been observed in at least 6 individuals who underwent testing for RASopathies (PS4 not met; GeneDx, LMM internal data; GTR ID's: 26957, 21766; SCV000063150.4, SCV000170190.9). This variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx internal data, SCV000170190.9). In summary, this variant meets criteria to be classified as likely benign for autosomal dominant RASopathies based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy Variant Curation Expert Panel: BP5, BP7 (Specification Version 2.1, 09/17/2024)

BP5

This variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx internal data, SCV000170190.9).

BP7

This variant is a synonymous (silent) variant at a nucleotide that is not highly conserved and is not predicted to impact splicing (BP7).

PS4

The c.*8C>T variant has been observed in at least 6 individuals who underwent testing for RASopathies (PS4 not met; GeneDx, LMM internal data; GTR ID's: 26957, 21766; SCV000063150.4, SCV000170190.9).

PM2

The filtering allele frequency in gnomAD v4.1.0 is 0.01257%(172/1145270 alleles) in non-Finnish European population (PM2_Supporting/BS1/BA1 are not met).

BA1

The filtering allele frequency in gnomAD v4.1.0 is 0.01257%(172/1145270 alleles) in non-Finnish European population (PM2_Supporting/BS1/BA1 are not met).

BS1

The filtering allele frequency in gnomAD v4.1.0 is 0.01257%(172/1145270 alleles) in non-Finnish European population (PM2_Supporting/BS1/BA1 are not met).

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