9-2717676-T-G

Variant summary

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

The NM_133497.4(KCNV2):c.-64T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,604,192 control chromosomes in the GnomAD database, including 38,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2718 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36044 hom.)
• Consequence: KCNV2 NM_133497.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0490

Genes affected

KCNV2 (HGNC:19698): (potassium voltage-gated channel modifier subfamily V member 2) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium voltage-gated channel subfamily V. This member is identified as a 'silent subunit', and it does not form homomultimers, but forms heteromultimers with several other subfamily members. Through obligatory heteromerization, it exerts a function-altering effect on other potassium channel subunits. This protein is strongly expressed in pancreas and has a weaker expression in several other tissues. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 9-2717676-T-G is Benign according to our data. Variant chr9-2717676-T-G is described in ClinVar as [Benign]. Clinvar id is 366402.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2717676-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNV2	NM_133497.4	c.-64T>G		5_prime_UTR_variant	1/2	ENST00000382082.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNV2	ENST00000382082.4	c.-64T>G		5_prime_UTR_variant	1/2	1	NM_133497.4	P1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26531 AN: 152012 Hom.: 2720 Cov.: 32

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.215 AC: 312813 AN: 1452062 Hom.: 36044 Cov.: 27 AF XY: 0.221 AC XY: 160141 AN XY: 723068

Gnomad4 AFR exome AF: 0.0658

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.174 AC: 26522 AN: 152130 Hom.: 2718 Cov.: 32 AF XY: 0.177 AC XY: 13177 AN XY: 74360

Gnomad4 AFR AF: 0.0707

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.206

Alfa AF: 0.200 Hom.: 652

Bravo AF: 0.164

Asia WGS AF: 0.288 AC: 1000 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cone dystrophy with supernormal rod response Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.6
Dann	Benign	0.74

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: rs11793555; hg19: chr9-2717676; COSMIC: COSV66056360; COSMIC: COSV66056360;