Variant 5-151253115-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000523466.5(GM2A):c.127-6640A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 882,268 control chromosomes in the GnomAD database, including 58,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10624 hom., cov: 32)

Exomes 𝑓: 0.36 ( 47834 hom. )

Consequence

GM2A
ENST00000523466.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.249

Variant links:

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]

GM2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 5-151253115-A-G is Benign according to our data. Variant chr5-151253115-A-G is described in ClinVar as [Benign]. Clinvar id is 352249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GM2A	ENST00000523466.5 linkuse as main transcript	c.127-6640A>G		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55897

AN:

151916

Hom.:

10596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.408

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.470

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.384

GnomAD4 exome

AF:

0.356

AC:

260035

AN:

730234

Hom.:

47834

Cov.:

AF XY:

0.354

AC XY:

137973

AN XY:

389626

show subpopulations

Gnomad4 AFR exome

AF:

0.411

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.458

Gnomad4 EAS exome

AF:

0.508

Gnomad4 SAS exome

AF:

0.358

Gnomad4 FIN exome

AF:

0.310

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.368

AC:

55985

AN:

152034

Hom.:

10624

Cov.:

AF XY:

0.371

AC XY:

27573

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.408

Gnomad4 AMR

AF:

0.455

Gnomad4 ASJ

AF:

0.448

Gnomad4 EAS

AF:

0.471

Gnomad4 SAS

AF:

0.364

Gnomad4 FIN

AF:

0.304

Gnomad4 NFE

AF:

0.323

Gnomad4 OTH

AF:

0.388

Alfa

AF:

0.343

Hom.:

3332

Bravo

AF:

0.385

Asia WGS

AF:

0.394

AC:

1368

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.7

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over