rs749909

Variant names:

• chr21-44434924-G-A
• rs749909
• NM_003307.4:c.3975-207G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-44434924-G-A
• chr21-44434924-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001320350.2(TRPM2):​c.4125-207G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 152,062 control chromosomes in the GnomAD database, including 52,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.83 (52578 hom., cov: 32)
• Consequence: TRPM2 NM_001320350.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.946
• 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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 21-44434924-G-A is Benign according to our data. Variant chr21-44434924-G-A is described in ClinVar as Benign. ClinVar VariationId is 1277010.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320350.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM2	NM_003307.4	MANE Select	c.3975-207G>A		intron	N/A	NP_003298.2
	TRPM2	NM_001320350.2		c.4125-207G>A		intron	N/A	NP_001307279.2
	TRPM2	NM_001433516.1		c.3975-207G>A		intron	N/A	NP_001420445.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM2	ENST00000397928.6	TSL:1 MANE Select	c.3975-207G>A		intron	N/A	ENSP00000381023.1
	TRPM2	ENST00000397932.6	TSL:1	c.4125-207G>A		intron	N/A	ENSP00000381026.2
	TRPM2	ENST00000300482.9	TSL:1	c.3975-207G>A		intron	N/A	ENSP00000300482.5

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126172 AN: 151944 Hom.: 52545 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.830 AC: 126264 AN: 152062 Hom.: 52578 Cov.: 32 AF XY: 0.830 AC XY: 61679 AN XY: 74338

African (AFR) AF: 0.853 AC: 35332 AN: 41436

American (AMR) AF: 0.842 AC: 12877 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2755 AN: 3472

East Asian (EAS) AF: 0.934 AC: 4833 AN: 5174

South Asian (SAS) AF: 0.834 AC: 4027 AN: 4828

European-Finnish (FIN) AF: 0.813 AC: 8607 AN: 10588

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.811 AC: 55110 AN: 67948

Other (OTH) AF: 0.838 AC: 1769 AN: 2112

Alfa AF: 0.815 Hom.: 31819

Bravo AF: 0.834

Asia WGS AF: 0.869 AC: 3023 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.20
DANN	Benign	0.35
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749909; hg19: chr21-45854807;