rs1618355

Variant names:

• chr21-44406579-C-A
• rs1618355
• NM_003307.4:c.2791-15C>A

Your query was ambiguous. Multiple possible variants found:

• chr21-44406579-C-A
• chr21-44406579-C-G
• chr21-44406579-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001320350.2(TRPM2):​c.2791-15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 1,602,260 control chromosomes in the GnomAD database, including 445,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38674 hom., cov: 32)
  • Exomes 𝑓: 0.75 (407026 hom.)
• Consequence: TRPM2 NM_001320350.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.150
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 21-44406579-C-A is Benign according to our data. Variant chr21-44406579-C-A is described in ClinVar as Benign. ClinVar VariationId is 1265082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 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.2791-15C>A		intron	N/A	NP_003298.2
	TRPM2	NM_001320350.2		c.2791-15C>A		intron	N/A	NP_001307279.2
	TRPM2	NM_001433516.1		c.2791-15C>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.2791-15C>A		intron	N/A	ENSP00000381023.1
	TRPM2	ENST00000397932.6	TSL:1	c.2791-15C>A		intron	N/A	ENSP00000381026.2
	TRPM2	ENST00000300482.9	TSL:1	c.2791-15C>A		intron	N/A	ENSP00000300482.5

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107695 AN: 151748 Hom.: 38674 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.730

GnomAD2 exomes AF: 0.728 AC: 172785 AN: 237226 AF XY: 0.728

Gnomad AFR exome AF: 0.590

Gnomad AMR exome AF: 0.716

Gnomad ASJ exome AF: 0.721

Gnomad EAS exome AF: 0.791

Gnomad FIN exome AF: 0.754

Gnomad NFE exome AF: 0.759

Gnomad OTH exome AF: 0.740

GnomAD4 exome AF: 0.748 AC: 1084843 AN: 1450394 Hom.: 407026 Cov.: 50 AF XY: 0.746 AC XY: 538158 AN XY: 721486

African (AFR) AF: 0.584 AC: 19497 AN: 33398

American (AMR) AF: 0.722 AC: 31363 AN: 43430

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 18648 AN: 25870

East Asian (EAS) AF: 0.746 AC: 29570 AN: 39618

South Asian (SAS) AF: 0.655 AC: 56162 AN: 85722

European-Finnish (FIN) AF: 0.754 AC: 36033 AN: 47774

Middle Eastern (MID) AF: 0.725 AC: 3633 AN: 5012

European-Non Finnish (NFE) AF: 0.762 AC: 845700 AN: 1109498

Other (OTH) AF: 0.736 AC: 44237 AN: 60072

GnomAD4 genome AF: 0.709 AC: 107728 AN: 151866 Hom.: 38674 Cov.: 32 AF XY: 0.707 AC XY: 52502 AN XY: 74224

African (AFR) AF: 0.589 AC: 24396 AN: 41388

American (AMR) AF: 0.747 AC: 11381 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2489 AN: 3468

East Asian (EAS) AF: 0.769 AC: 3944 AN: 5128

South Asian (SAS) AF: 0.650 AC: 3134 AN: 4820

European-Finnish (FIN) AF: 0.747 AC: 7900 AN: 10576

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52065 AN: 67932

Other (OTH) AF: 0.729 AC: 1539 AN: 2112

Alfa AF: 0.731 Hom.: 8049

Bravo AF: 0.704

Asia WGS AF: 0.673 AC: 2344 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.45
PhyloP100		0.15
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: rs1618355; hg19: chr21-45826462;