20-48995838-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_006420.3(ARFGEF2):c.3177G>A(p.Ser1059=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,614,148 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts 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. S1059S) has been classified as Likely benign.
Frequency
Consequence
NM_006420.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARFGEF2 | NM_006420.3 | c.3177G>A | p.Ser1059= | synonymous_variant | 23/39 | ENST00000371917.5 | |
ARFGEF2 | NM_001410846.1 | c.3174G>A | p.Ser1058= | synonymous_variant | 23/39 | ||
ARFGEF2 | XM_047439832.1 | c.2613G>A | p.Ser871= | synonymous_variant | 21/37 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARFGEF2 | ENST00000371917.5 | c.3177G>A | p.Ser1059= | synonymous_variant | 23/39 | 1 | NM_006420.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00760 AC: 1156AN: 152172Hom.: 10 Cov.: 32
GnomAD3 exomes AF: 0.00784 AC: 1972AN: 251492Hom.: 17 AF XY: 0.00812 AC XY: 1103AN XY: 135920
GnomAD4 exome AF: 0.0107 AC: 15599AN: 1461858Hom.: 88 Cov.: 31 AF XY: 0.0105 AC XY: 7643AN XY: 727236
GnomAD4 genome AF: 0.00758 AC: 1155AN: 152290Hom.: 10 Cov.: 32 AF XY: 0.00755 AC XY: 562AN XY: 74466
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 21, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 30, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | ARFGEF2: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Periventricular heterotopia with microcephaly, autosomal recessive 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at