rs76784312
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000112.4(SLC26A2):āc.229A>Cā(p.Asn77His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,614,196 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000112.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A2 | NM_000112.4 | c.229A>C | p.Asn77His | missense_variant | 2/3 | ENST00000286298.5 | |
SLC26A2 | XM_017009191.3 | c.229A>C | p.Asn77His | missense_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A2 | ENST00000286298.5 | c.229A>C | p.Asn77His | missense_variant | 2/3 | 1 | NM_000112.4 | P1 | |
SLC26A2 | ENST00000690410.1 | n.461A>C | non_coding_transcript_exon_variant | 2/2 |
Frequencies
GnomAD3 genomes AF: 0.00146 AC: 222AN: 152214Hom.: 4 Cov.: 32
GnomAD3 exomes AF: 0.00459 AC: 1152AN: 251114Hom.: 20 AF XY: 0.00624 AC XY: 848AN XY: 135838
GnomAD4 exome AF: 0.00231 AC: 3371AN: 1461864Hom.: 68 Cov.: 33 AF XY: 0.00331 AC XY: 2409AN XY: 727238
GnomAD4 genome AF: 0.00145 AC: 221AN: 152332Hom.: 4 Cov.: 32 AF XY: 0.00211 AC XY: 157AN XY: 74494
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 09, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 02, 2017 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 10, 2021 | - - |
Achondrogenesis, type IB Benign:3
Benign, 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 10, 2020 | - - |
Multiple epiphyseal dysplasia type 4 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 03, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | SLC26A2: BS1, BS2 - |
Diastrophic dysplasia Benign:2
Benign, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | - | The heterozygous p.Asn77His variant in SLC26A2 has been identified in at least 1 individual with diastrophic dysplasia (PMID: 11241838, 21228398), and has been identified in >3% of South Asian chromosomes and 13 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive diastrophic dysplasia. - |
Benign, 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Atelosteogenesis type II Benign:1
Benign, 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Diastrophic dysplasia;C0265274:Achondrogenesis, type IB;C1847593:Multiple epiphyseal dysplasia type 4;C1850554:Atelosteogenesis type II Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Sulfate transporter-related osteochondrodysplasia Benign:1
Benign, 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at