rs2838553

Variant names:

• chr21-44358411-T-A
• rs2838553
• NM_003307.4:c.254+3675T>A

Variant summary

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

The NM_003307.4(TRPM2):​c.254+3675T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,966 control chromosomes in the GnomAD database, including 5,419 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 0.25 (5419 hom., cov: 32)
• Consequence: TRPM2 NM_003307.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795
• Publications: 6 publications found

Genes affected

TRPM2 (HGNC:12339): (transient receptor potential cation channel subfamily M member 2) The protein encoded by this gene forms a tetrameric cation channel that is permeable to calcium, sodium, and potassium and is regulated by free intracellular ADP-ribose. The encoded protein is activated by oxidative stress and confers susceptibility to cell death. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. Additional transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2016]

ENSG00000302477 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM2	NM_003307.4	c.254+3675T>A		intron_variant	Intron 2 of 31	ENST00000397928.6	NP_003298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM2	ENST00000397928.6	c.254+3675T>A		intron_variant	Intron 2 of 31	1	NM_003307.4	ENSP00000381023.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38483 AN: 151848 Hom.: 5411 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.254 AC: 38537 AN: 151966 Hom.: 5419 Cov.: 32 AF XY: 0.251 AC XY: 18629 AN XY: 74274

African (AFR) AF: 0.389 AC: 16114 AN: 41414

American (AMR) AF: 0.210 AC: 3215 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 522 AN: 3472

East Asian (EAS) AF: 0.120 AC: 621 AN: 5162

South Asian (SAS) AF: 0.158 AC: 761 AN: 4824

European-Finnish (FIN) AF: 0.273 AC: 2883 AN: 10544

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13738 AN: 67956

Other (OTH) AF: 0.198 AC: 417 AN: 2106

Alfa AF: 0.224 Hom.: 525

Bravo AF: 0.257

Asia WGS AF: 0.168 AC: 587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.80
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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: rs2838553; hg19: chr21-45778294;