20-49017281-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBS1_Supporting
The NM_006420.3(ARFGEF2):c.4348T>A(p.Cys1450Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,014 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 Uncertain significance (★).
Frequency
Consequence
NM_006420.3 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARFGEF2 | NM_006420.3 | c.4348T>A | p.Cys1450Ser | missense_variant | Exon 32 of 39 | ENST00000371917.5 | NP_006411.2 | |
ARFGEF2 | NM_001410846.1 | c.4345T>A | p.Cys1449Ser | missense_variant | Exon 32 of 39 | NP_001397775.1 | ||
ARFGEF2 | XM_047439832.1 | c.3784T>A | p.Cys1262Ser | missense_variant | Exon 30 of 37 | XP_047295788.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251288Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135822
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461728Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727154
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74454
ClinVar
Submissions by phenotype
Periventricular heterotopia with microcephaly, autosomal recessive Uncertain:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at