rs267606643
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PS1_ModeratePM2PP3_ModeratePP5_Moderate
The NM_001625.4(AK2):āc.494A>Gā(p.Asp165Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.
Frequency
Consequence
NM_001625.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AK2 | NM_001625.4 | c.494A>G | p.Asp165Gly | missense_variant | 5/6 | ENST00000672715.1 | NP_001616.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AK2 | ENST00000672715.1 | c.494A>G | p.Asp165Gly | missense_variant | 5/6 | NM_001625.4 | ENSP00000499935 | P3 | ||
ENST00000427524.1 | n.246-16509T>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460124Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726366
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Reticular dysgenesis Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 03, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 165 of the AK2 protein (p.Asp165Gly). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 18256). This variant is also known as c.546A>G. This missense change has been observed in individual(s) with severe combined immunodeficiency (PMID: 19043416). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2009 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at