rs778232785
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_002180.3(IGHMBP2):c.4G>A(p.Ala2Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,566,354 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2S) has been classified as Uncertain significance.
Frequency
Consequence
NM_002180.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGHMBP2 | NM_002180.3 | c.4G>A | p.Ala2Thr | missense_variant | 1/15 | ENST00000255078.8 | |
IGHMBP2 | XM_047426881.1 | c.4G>A | p.Ala2Thr | missense_variant | 1/15 | ||
IGHMBP2 | XM_017017671.3 | c.4G>A | p.Ala2Thr | missense_variant | 1/12 | ||
IGHMBP2 | XM_005273976.3 | c.4G>A | p.Ala2Thr | missense_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGHMBP2 | ENST00000255078.8 | c.4G>A | p.Ala2Thr | missense_variant | 1/15 | 1 | NM_002180.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152246Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.0000408 AC: 7AN: 171622Hom.: 0 AF XY: 0.0000650 AC XY: 6AN XY: 92358
GnomAD4 exome AF: 0.0000212 AC: 30AN: 1414108Hom.: 0 Cov.: 44 AF XY: 0.0000314 AC XY: 22AN XY: 699612
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152246Hom.: 0 Cov.: 35 AF XY: 0.0000269 AC XY: 2AN XY: 74382
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 | - | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 11, 2021 | The p.A2T variant (also known as c.4G>A), located in coding exon 1 of the IGHMBP2 gene, results from a G to A substitution at nucleotide position 4. The alanine at codon 2 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at