rs1800742
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000548.5(TSC2):c.1110G>A(p.Gln370Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,613,538 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000548.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00817 AC: 1243AN: 152174Hom.: 9 Cov.: 33
GnomAD3 exomes AF: 0.0100 AC: 2511AN: 250212Hom.: 19 AF XY: 0.0101 AC XY: 1373AN XY: 135582
GnomAD4 exome AF: 0.0108 AC: 15849AN: 1461246Hom.: 113 Cov.: 32 AF XY: 0.0107 AC XY: 7781AN XY: 726922
GnomAD4 genome AF: 0.00814 AC: 1240AN: 152292Hom.: 9 Cov.: 33 AF XY: 0.00780 AC XY: 581AN XY: 74456
ClinVar
Submissions by phenotype
not specified Benign:8
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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. -
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Gln370Gln in exon 11 of TSC2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1.5% (125/8600) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs1800742). -
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Tuberous sclerosis 2 Benign:5
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not provided Benign:4
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Variant summary: The c.1110G>A (p.Gln370=) in TSC2 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.01 predominantly in individuals of European descent (0.016; 1083/65734) including 12 homozygous spread through 4 out of 6 populations. The variant of interest has been reported as polymorphism via publications and cited as Benign by multiple reputable databases/clinical laboratories. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign. -
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TSC2: BP4, BP7, BS1, BS2 -
Tuberous sclerosis syndrome Benign:2Other:1
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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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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Hereditary cancer-predisposing syndrome Benign:1
This alteration is classified as 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