rs1753618021

Variant names:

• chr5-151253134-C-A
• rs1753618021
• ENST00000523466.5:c.127-6621C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-151253134-C-A
• chr5-151253134-C-G
• chr5-151253134-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000523466.5(GM2A):​c.127-6621C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000115 in 869,686 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: GM2A ENST00000523466.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GM2A	NM_000405.5	c.-83C>A		upstream_gene_variant		ENST00000357164.4	NP_000396.2
GM2A	NM_001167607.3	c.-83C>A		upstream_gene_variant			NP_001161079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GM2A	ENST00000523466.5	c.127-6621C>A		intron_variant	Intron 2 of 3	3		ENSP00000429100.1
GM2A	ENST00000357164.4	c.-83C>A		upstream_gene_variant		1	NM_000405.5	ENSP00000349687.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000115 AC: 1 AN: 869686 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 456294

African (AFR) AF: 0.00 AC: 0 AN: 22052

American (AMR) AF: 0.00 AC: 0 AN: 43800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22428

East Asian (EAS) AF: 0.00 AC: 0 AN: 36906

South Asian (SAS) AF: 0.00 AC: 0 AN: 74400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3784

European-Non Finnish (NFE) AF: 0.00000174 AC: 1 AN: 574228

Other (OTH) AF: 0.00 AC: 0 AN: 40968

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.72
PhyloP100		0.45
PromoterAI		-0.47	Neutral

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

Other links and lift over

dbSNP: rs1753618021; hg19: chr5-150632695;