Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000466681 | SCV000616575 | benign | RASopathy | 2017-05-09 | reviewed by expert panel | curation | The filtering allele frequency of the c.603C>T (p.Leu201=) variant in the MAP2K2 gene is 0.191% (18/6102) of African chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581) |
Laboratory for Molecular Medicine, |
RCV000039489 | SCV000063177 | likely benign | not specified | 2009-01-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000466681 | SCV000561667 | benign | RASopathy | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000039489 | SCV000917612 | benign | not specified | 2018-06-04 | criteria provided, single submitter | clinical testing | Variant summary: MAP2K2 c.603C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was observed with an allele frequency of 0.00028 in 265334 control chromosomes (gnomAD). The observed variant frequency within African control individuals in the gnomAD database is approximately 920-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in MAP2K2 causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.603C>T in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. A co-occurrence with other pathogenic variant has been reported (PTPN11 c.182A>G, p.Asp61Gly) in an internal specimen, providing supporting evidence for a benign role. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign. |
Gene |
RCV001705635 | SCV001860429 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV001813315 | SCV002060580 | likely benign | Noonan syndrome and Noonan-related syndrome | 2019-02-01 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001705635 | SCV004698564 | likely benign | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | MAP2K2: BS1 |
Prevention |
RCV003894846 | SCV004726235 | benign | MAP2K2-related condition | 2019-06-19 | criteria provided, single submitter | clinical testing | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |