rs200729207
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001164507.2(NEB):c.8644G>A(p.Asp2882Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000711 in 1,613,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. D2882D) has been classified as Benign.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.8644G>A | p.Asp2882Asn | missense_variant | 61/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.8644G>A | p.Asp2882Asn | missense_variant | 61/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.8644G>A | p.Asp2882Asn | missense_variant | 61/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.8644G>A | p.Asp2882Asn | missense_variant | 61/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.8644G>A | p.Asp2882Asn | missense_variant | 61/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000401 AC: 61AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000341 AC: 85AN: 249102Hom.: 0 AF XY: 0.000355 AC XY: 48AN XY: 135132
GnomAD4 exome AF: 0.000743 AC: 1086AN: 1461684Hom.: 0 Cov.: 32 AF XY: 0.000729 AC XY: 530AN XY: 727124
GnomAD4 genome ? AF: 0.000401 AC: 61AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24AN XY: 74316
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 15, 2022 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 05, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 25, 2023 | - - |
Nemaline myopathy 2 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 2882 of the NEB protein (p.Asp2882Asn). This variant is present in population databases (rs200729207, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with NEB-related conditions. ClinVar contains an entry for this variant (Variation ID: 198308). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 01, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 29, 2024 | Variant summary: NEB c.8644G>A (p.Asp2882Asn) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00034 in 249102 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in NEB causing Nemaline Myopathy 2 (0.00034 vs 0.0035), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.8644G>A in individuals affected with Nemaline Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 198308). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at