rs1785467

Positions:

• chr21-44418749-C-T
• chr21-44418749-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003307.4(TRPM2):​c.3461+194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,146 control chromosomes in the GnomAD database, including 60,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.89 (60591 hom., cov: 32)
• Consequence: TRPM2 NM_003307.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.141

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]

TRPM2-AS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 21-44418749-C-T is Benign according to our data. Variant chr21-44418749-C-T is described in ClinVar as [Benign]. Clinvar id is 1245588.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM2	NM_003307.4	c.3461+194C>T		intron_variant		ENST00000397928.6	NP_003298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM2	ENST00000397928.6	c.3461+194C>T		intron_variant		1	NM_003307.4	ENSP00000381023.1

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135600 AN: 152028 Hom.: 60549 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.898

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

GnomAD4 genome AF: 0.892 AC: 135701 AN: 152146 Hom.: 60591 Cov.: 32 AF XY: 0.892 AC XY: 66333 AN XY: 74390

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.861

Gnomad4 ASJ AF: 0.871

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.858

Gnomad4 NFE AF: 0.874

Gnomad4 OTH AF: 0.897

Alfa AF: 0.897 Hom.: 8062

Bravo AF: 0.893

Asia WGS AF: 0.915 AC: 3182 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.93

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

LitVar

Other links and lift over

dbSNP: rs1785467; hg19: chr21-45838632;