Variant rs2075783 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000523004.1(GM2A):c.*294A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,589,246 control chromosomes in the GnomAD database, including 62,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 4856 hom., cov: 32)

Exomes 𝑓: 0.28 ( 57217 hom. )

Consequence

GM2A
ENST00000523004.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-151267219-A-C is Benign according to our data. Variant chr5-151267219-A-C is described in ClinVar as [Benign]. Clinvar id is 1234926.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GM2A	NM_000405.5 linkuse as main transcript	c.427-77A>C		intron_variant		ENST00000357164.4	NP_000396.2	P17900
GM2A	NM_001167607.3 linkuse as main transcript	c.413-273A>C		intron_variant			NP_001161079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GM2A	ENST00000523004.1 linkuse as main transcript	c.*294A>C		3_prime_UTR_variant	2/2	1		ENSP00000430541.1		H0YBY3
GM2A	ENST00000357164.4 linkuse as main transcript	c.427-77A>C		intron_variant		1	NM_000405.5	ENSP00000349687.3		P17900

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34317

AN:

152084

Hom.:

4849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0584

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.264

GnomAD4 exome

AF:

0.276

AC:

396094

AN:

1437044

Hom.:

57217

Cov.:

AF XY:

0.277

AC XY:

198415

AN XY:

715446

show subpopulations

Gnomad4 AFR exome

AF:

0.0550

Gnomad4 AMR exome

AF:

0.492

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.278

Gnomad4 SAS exome

AF:

0.330

Gnomad4 FIN exome

AF:

0.247

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.273

GnomAD4 genome

AF:

0.226

AC:

34330

AN:

152202

Hom.:

4856

Cov.:

AF XY:

0.230

AC XY:

17143

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0582

Gnomad4 AMR

AF:

0.385

Gnomad4 ASJ

AF:

0.328

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.339

Gnomad4 FIN

AF:

0.240

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.258

Hom.:

2551

Bravo

AF:

0.231

Asia WGS

AF:

0.265

AC:

919

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.88

CADD

Benign

1.7

DANN

Benign

0.38

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