chr5-151253173-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000523466.5(GM2A):c.127-6582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,440,642 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.011 ( 27 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 24 hom. )
Consequence
GM2A
ENST00000523466.5 intron
ENST00000523466.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0220
Genes affected
GM2A (HGNC:4367): (ganglioside GM2 activator) This gene encodes a small glycolipid transport protein which acts as a substrate specific co-factor for the lysosomal enzyme beta-hexosaminidase A. Beta-hexosaminidase A, together with GM2 ganglioside activator, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Mutations in this gene result in GM2-gangliosidosis type AB or the AB variant of Tay-Sachs disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 5-151253173-G-A is Benign according to our data. Variant chr5-151253173-G-A is described in ClinVar as [Benign]. Clinvar id is 352250.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1604/152264) while in subpopulation AFR AF= 0.0362 (1502/41542). AF 95% confidence interval is 0.0346. There are 27 homozygotes in gnomad4. There are 757 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 27 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GM2A | NM_000405.5 | upstream_gene_variant | ENST00000357164.4 | ||||
GM2A | NM_001167607.3 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GM2A | ENST00000523466.5 | c.127-6582G>A | intron_variant | 3 | |||||
GM2A | ENST00000357164.4 | upstream_gene_variant | 1 | NM_000405.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0105 AC: 1605AN: 152146Hom.: 27 Cov.: 32
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GnomAD3 exomes AF: 0.00282 AC: 707AN: 251130Hom.: 14 AF XY: 0.00210 AC XY: 285AN XY: 135782
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GnomAD4 exome AF: 0.00107 AC: 1382AN: 1288378Hom.: 24 Cov.: 19 AF XY: 0.000914 AC XY: 594AN XY: 649974
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GnomAD4 genome AF: 0.0105 AC: 1604AN: 152264Hom.: 27 Cov.: 32 AF XY: 0.0102 AC XY: 757AN XY: 74442
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Tay-Sachs disease, variant AB Benign:1
Benign, 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 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at