chr11-68939621-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_002180.3(IGHMBP2):āc.2872A>Gā(p.Asn958Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000314 in 1,613,430 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. N958N) has been classified as Likely benign.
Frequency
Consequence
NM_002180.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGHMBP2 | NM_002180.3 | c.2872A>G | p.Asn958Asp | missense_variant | 15/15 | ENST00000255078.8 | |
IGHMBP2 | XM_017017670.3 | c.1861A>G | p.Asn621Asp | missense_variant | 11/11 | ||
IGHMBP2 | XM_005273975.4 | c.1744A>G | p.Asn582Asp | missense_variant | 8/8 | ||
IGHMBP2 | XM_011544994.2 | c.1639A>G | p.Asn547Asp | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGHMBP2 | ENST00000255078.8 | c.2872A>G | p.Asn958Asp | missense_variant | 15/15 | 1 | NM_002180.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000348 AC: 53AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000572 AC: 143AN: 250136Hom.: 0 AF XY: 0.000568 AC XY: 77AN XY: 135472
GnomAD4 exome AF: 0.000311 AC: 454AN: 1461212Hom.: 1 Cov.: 31 AF XY: 0.000307 AC XY: 223AN XY: 726930
GnomAD4 genome AF: 0.000348 AC: 53AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21AN XY: 74374
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Autosomal recessive distal spinal muscular atrophy 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Autosomal recessive distal spinal muscular atrophy 1;C4015349:Charcot-Marie-Tooth disease axonal type 2S Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 15, 2020 | This variant is associated with the following publications: (PMID: 32376792) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at