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]

Variant: NM_002755.3(MAP2K1):c.694-8_694-7dupTC

Curation Version - 1.2
Curation History
JSON LD for Version 1.2

CA147595

94082 (ClinVar)

Gene: MAP2K1

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 683b32d2-f588-4a79-be69-e8717aa258d0

Approved on: 2024-09-17

Published on: 2024-10-01

HGVS expressions

NM_002755.3:c.694-8_694-7dupTC

NM_002755.3:c.694-7_694-6insTC

NM_002755.3(MAP2K1):c.694-8_694-7dupTC

NC_000015.10:g.66484982_66484983dup

CM000677.2:g.66484982_66484983dup

NC_000015.9:g.66777320_66777321dup

CM000677.1:g.66777320_66777321dup

NC_000015.8:g.64564374_64564375dup

NG_008305.1:g.103110_103111dup

ENST00000684779.1:c.628-2246_628-2245dup

ENST00000685172.1:c.694-8_694-7dup

ENST00000685763.1:c.547-8_547-7dup

ENST00000686347.1:c.569-2246_569-2245dup

ENST00000687191.1:n.1052-8_1052-7dup

ENST00000687481.1:n.101_102dup

ENST00000689951.1:c.745-8_745-7dup

ENST00000691077.1:c.694-12_694-11dup

ENST00000691576.1:c.569-12_569-11dup

ENST00000691937.1:c.694-8_694-7dup

ENST00000692487.1:c.694-12_694-11dup

ENST00000692683.1:c.628-8_628-7dup

ENST00000693150.1:c.550-8_550-7dup

ENST00000307102.10:c.694-8_694-7dup

ENST00000307102.9:c.694-8_694-7dup

ENST00000566326.1:c.166-8_166-7dup

NM_002755.3:c.694-8_694-7dup

NM_002755.4:c.694-8_694-7dup

Benign

BA1 BP7 BP5

PP3 PM2 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 MAP2K1 Version 2.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.694-8_694-7dupTC variant is an intronic variant located in intron 6 of the MAP2K1 gene. The filtering allele frequency in gnomAD v4.1.0 is 4.669% (3488/74934 alleles) in the African/African American population, which meets the threshold to apply BA1. The computational predictor SpliceAI predicts no impact on splicing (BP7). This variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx, Partners LMM, EGL genetics internal data 26957, 21766, 500060; ClinVar SCV000111925.5; SCV000204171.4; SCV000207934.6). In summary, this variant meets criteria to be classified as benign for autosomal dominant RASopathies based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy Variant Curation Expert Panel: BA1, BP5, BP7 (Specification Version 2.1, 09/17/2024)

BA1

The filtering allele frequency in gnomAD v4.1.0 is 4.669% (3488/74934 alleles) in the African/African American population, which meets the threshold to apply BA1.

BP7

The computational predictor SpliceAI predicts no impact on splicing (BP7).

BP5

This variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx, Partners LMM, EGL genetics internal data 26957, 21766, 500060; ClinVar SCV000111925.5; SCV000204171.4; SCV000207934.6).

PP3

SpliceAI predicts no impact on splicing (BP7)

PM2

The filtering allele frequency in gnomAD v4.1.0 is 4.669% (3488/74934 alleles) in the African/African American population, which meets the threshold to apply BA1.

BS1

The filtering allele frequency in gnomAD v4.1.0 is 4.669% (3488/74934 alleles) in the African/African American population, which meets the threshold to apply BA1.

Curation History

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