rs144248214
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The ENST00000278947.6(SCN2B):c.629C>T(p.Pro210Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,613,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P210P) has been classified as Likely benign.
Frequency
Consequence
ENST00000278947.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN2B | NM_004588.5 | c.629C>T | p.Pro210Leu | missense_variant | 4/4 | ENST00000278947.6 | NP_004579.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN2B | ENST00000278947.6 | c.629C>T | p.Pro210Leu | missense_variant | 4/4 | 1 | NM_004588.5 | ENSP00000278947 | P1 | |
SCN2B | ENST00000669850.1 | n.871C>T | non_coding_transcript_exon_variant | 4/4 | ||||||
SCN2B | ENST00000658882.1 | c.*454C>T | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 | ENSP00000499572 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152090Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251418Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135890
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1461774Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37AN XY: 727190
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74286
ClinVar
Submissions by phenotype
Atrial fibrillation, familial, 14 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 28, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 08, 2024 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 210 of the SCN2B protein (p.Pro210Leu). This variant is present in population databases (rs144248214, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SCN2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 191493). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 21, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at