5-151267479-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

Tay-Sachs disease AB variant
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), ClinGen

GM2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
GM2A	NM_000405.5 link	c.*28C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000357164.4	NP_000396.2	P17900
GM2A	NM_001167607.3 link	c.413-13C>T		intron_variant	Intron 3 of 3		NP_001161079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GM2A	ENST00000357164.4 link	c.*28C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_000405.5	ENSP00000349687.3		P17900
GM2A	ENST00000523004.1 link	c.*554C>T		downstream_gene_variant		1		ENSP00000430541.1		H0YBY3

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

GnomAD2 exomes

AF:

0.0716

AC:

17956

AN:

250922

AF XY:

0.0684

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 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

African (AFR)

AF:

0.198

AC:

6627

AN:

33450

American (AMR)

AF:

0.0692

AC:

3093

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0289

AC:

755

AN:

26130

East Asian (EAS)

AF:

0.250

AC:

9934

AN:

39690

South Asian (SAS)

AF:

0.0854

AC:

7360

AN:

86216

European-Finnish (FIN)

AF:

0.0439

AC:

2340

AN:

53360

Middle Eastern (MID)

AF:

0.0309

AC:

178

AN:

5768

European-Non Finnish (NFE)

AF:

0.0292

AC:

32477

AN:

1111784

Other (OTH)

AF:

0.0630

AC:

3803

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

3347

6693

10040

13386

16733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1516

3032

4548

6064

7580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0889

AC:

13528

AN:

152210

Hom.:

1089

Cov.:

AF XY:

0.0908

AC XY:

6759

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.193

AC:

8003

AN:

41524

American (AMR)

AF:

0.0680

AC:

1041

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0276

AC:

AN:

3472

East Asian (EAS)

AF:

0.259

AC:

1334

AN:

5156

South Asian (SAS)

AF:

0.0967

AC:

466

AN:

4820

European-Finnish (FIN)

AF:

0.0398

AC:

422

AN:

10602

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0294

AC:

1997

AN:

68020

Other (OTH)

AF:

0.0691

AC:

146

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

585

1170

1755

2340

2925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0553

Hom.:

170

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

Dec 16, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 18, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Tay-Sachs disease, variant AB

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.44

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over