17-16428313-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016113.5(TRPV2):c.1351-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,614,108 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00090 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (14 hom.)
• Consequence: TRPV2 NM_016113.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0006407
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.320

Genes affected

TRPV2 (HGNC:18082): (transient receptor potential cation channel subfamily V member 2) This gene encodes an ion channel that is activated by high temperatures above 52 degrees Celsius. The protein may be involved in transduction of high-temperature heat responses in sensory ganglia. It is thought that in other tissues the channel may be activated by stimuli other than heat. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-16428313-G-A is Benign according to our data. Variant chr17-16428313-G-A is described in ClinVar as [Benign]. Clinvar id is 771491.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV2	NM_016113.5	c.1351-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000338560.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV2	ENST00000338560.12	c.1351-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_016113.5	P1
	ENST00000441875.1	n.75-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5
TRPV2	ENST00000583241.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.000894 AC: 136 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00272 AC: 683 AN: 251446 Hom.: 4 AF XY: 0.00275 AC XY: 374 AN XY: 135900

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00842

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.000761

Gnomad SAS exome AF: 0.0103

Gnomad FIN exome AF: 0.000647

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00109 AC: 1589 AN: 1461802 Hom.: 14 Cov.: 32 AF XY: 0.00128 AC XY: 934 AN XY: 727222

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.00805

Gnomad4 ASJ exome AF: 0.00153

Gnomad4 EAS exome AF: 0.00232

Gnomad4 SAS exome AF: 0.00982

Gnomad4 FIN exome AF: 0.000768

Gnomad4 NFE exome AF: 0.000101

Gnomad4 OTH exome AF: 0.00149

GnomAD4 genome AF: 0.000900 AC: 137 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.000967 AC XY: 72 AN XY: 74468

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000458 Hom.: 0

Bravo AF: 0.00101

Asia WGS AF: 0.00982 AC: 34 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

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

Invitae

May 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	2.2
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00064
dbscSNV1_RF	Benign	0.078
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: rs201142576; hg19: chr17-16331627;