5-151225509-A-G

Variant names:

• chr5-151225509-A-G
• rs153462
• ENST00000523466.5:c.126+12620A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523466.5(GM2A):​c.126+12620A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,088 control chromosomes in the GnomAD database, including 6,118 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6118 hom., cov: 32)
• Consequence: GM2A ENST00000523466.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000523466.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GM2A	ENST00000523466.5	TSL:3	c.126+12620A>G		intron	N/A	ENSP00000429100.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42524 AN: 151970 Hom.: 6119 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.280 AC: 42544 AN: 152088 Hom.: 6118 Cov.: 32 AF XY: 0.285 AC XY: 21204 AN XY: 74344

African (AFR) AF: 0.256 AC: 10615 AN: 41490

American (AMR) AF: 0.306 AC: 4673 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3468

East Asian (EAS) AF: 0.460 AC: 2381 AN: 5172

South Asian (SAS) AF: 0.430 AC: 2074 AN: 4822

European-Finnish (FIN) AF: 0.320 AC: 3388 AN: 10580

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17553 AN: 67976

Other (OTH) AF: 0.278 AC: 586 AN: 2106

Alfa AF: 0.266 Hom.: 24322

Bravo AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.48
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs153462; hg19: chr5-150605070;