Variant rs9324685 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 NM_000405.5(GM2A):c.*28C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 1,613,684 control chromosomes in the GnomAD database, including 4,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 1089 hom., cov: 32)

Exomes 𝑓: 0.046 ( 3264 hom. )

Consequence

GM2A
NM_000405.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.35

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 5-151267479-C-T is Benign according to our data. Variant chr5-151267479-C-T is described in ClinVar as [Benign]. Clinvar id is 256029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GM2A	NM_000405.5 linkuse as main transcript	c.*28C>T		3_prime_UTR_variant	4/4	ENST00000357164.4
GM2A	NM_001167607.3 linkuse as main transcript	c.413-13C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GM2A	ENST00000357164.4 linkuse as main transcript	c.*28C>T		3_prime_UTR_variant	4/4	1	NM_000405.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0888

AC:

13508

AN:

152092

Hom.:

1086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0683

Gnomad ASJ

AF:

0.0276

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.0968

Gnomad FIN

AF:

0.0398

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0294

Gnomad OTH

AF:

0.0699

GnomAD3 exomes

AF:

0.0716

AC:

17956

AN:

250922

Hom.:

1252

AF XY:

0.0684

AC XY:

9279

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.0705

Gnomad ASJ exome

AF:

0.0289

Gnomad EAS exome

AF:

0.258

Gnomad SAS exome

AF:

0.0850

Gnomad FIN exome

AF:

0.0441

Gnomad NFE exome

AF:

0.0301

Gnomad OTH exome

AF:

0.0473

GnomAD4 exome

AF:

0.0455

AC:

66567

AN:

1461474

Hom.:

3264

Cov.:

AF XY:

0.0460

AC XY:

33477

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.198

Gnomad4 AMR exome

AF:

0.0692

Gnomad4 ASJ exome

AF:

0.0289

Gnomad4 EAS exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.0854

Gnomad4 FIN exome

AF:

0.0439

Gnomad4 NFE exome

AF:

0.0292

Gnomad4 OTH exome

AF:

0.0630

GnomAD4 genome

AF:

0.0889

AC:

13528

AN:

152210

Hom.:

1089

Cov.:

AF XY:

0.0908

AC XY:

6759

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.0680

Gnomad4 ASJ

AF:

0.0276

Gnomad4 EAS

AF:

0.259

Gnomad4 SAS

AF:

0.0967

Gnomad4 FIN

AF:

0.0398

Gnomad4 NFE

AF:

0.0294

Gnomad4 OTH

AF:

0.0691

Alfa

AF:

0.0511

Hom.:

155

Bravo

AF:

0.0954

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 16, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Tay-Sachs disease, variant AB

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.9

DANN

Benign

0.44

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