chr11-62690389-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001122955.4(BSCL2):c.1367G>A(p.Arg456His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 1,613,872 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001122955.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BSCL2 | NM_001122955.4 | c.1367G>A | p.Arg456His | missense_variant | Exon 11 of 11 | ENST00000360796.10 | NP_001116427.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BSCL2 | ENST00000360796.10 | c.1367G>A | p.Arg456His | missense_variant | Exon 11 of 11 | 1 | NM_001122955.4 | ENSP00000354032.5 | ||
HNRNPUL2-BSCL2 | ENST00000403734.2 | n.*1418G>A | non_coding_transcript_exon_variant | Exon 24 of 24 | 2 | ENSP00000456010.1 | ||||
HNRNPUL2-BSCL2 | ENST00000403734.2 | n.*1418G>A | 3_prime_UTR_variant | Exon 24 of 24 | 2 | ENSP00000456010.1 |
Frequencies
GnomAD3 genomes AF: 0.000178 AC: 27AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000322 AC: 81AN: 251404Hom.: 0 AF XY: 0.000419 AC XY: 57AN XY: 135884
GnomAD4 exome AF: 0.000280 AC: 410AN: 1461768Hom.: 1 Cov.: 32 AF XY: 0.000347 AC XY: 252AN XY: 727188
GnomAD4 genome AF: 0.000178 AC: 27AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74294
ClinVar
Submissions by phenotype
not provided Uncertain:5
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A variant of uncertain significance has been identified in the BSCL2 gene. The R392H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in 32/30780 (0.1%) alleles from individuals of South Asian background in large population cohorts (Lek et al., 2016). The R392H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -
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Hereditary spastic paraplegia Uncertain:1
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Monogenic diabetes Uncertain:1
ACMG Criteria: PP3 -
Inborn genetic diseases Benign:1
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. -
Charcot-Marie-Tooth disease type 2 Benign:1
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Congenital generalized lipodystrophy type 2 Other:1
Potent mutations in BSCL2 gene are associated with Congenital generalized lipodystrophy, type 2, which can present with insulin resistance, fatty liver and diabetes.However, the role of this particular variant rs149466797 of Congenital Generalized Lipodystrophy type 2 remains uncertain -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at