9-2717698-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_133497.4(KCNV2):c.-42C>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 0.575 in 1,613,100 control chromosomes in the GnomAD database, including 270,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28639 hom., cov: 32)
  • Exomes 𝑓: 0.57 (241426 hom.)
• Consequence: KCNV2 NM_133497.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.40

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.12).
• BP6: Variant 9-2717698-C-G is Benign according to our data. Variant chr9-2717698-C-G is described in ClinVar as [Benign]. Clinvar id is 366403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-2717698-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNV2	NM_133497.4	c.-42C>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.-42C>G		5_prime_UTR_variant	1/2	1	NM_133497.4	P1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92594 AN: 151870 Hom.: 28599 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.612

GnomAD3 exomes AF: 0.619 AC: 154411 AN: 249504 Hom.: 49007 AF XY: 0.609 AC XY: 82290 AN XY: 135172

Gnomad AFR exome AF: 0.669

Gnomad AMR exome AF: 0.776

Gnomad ASJ exome AF: 0.615

Gnomad EAS exome AF: 0.795

Gnomad SAS exome AF: 0.620

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.551

Gnomad OTH exome AF: 0.592

GnomAD4 exome AF: 0.571 AC: 834291 AN: 1461110 Hom.: 241426 Cov.: 41 AF XY: 0.572 AC XY: 415388 AN XY: 726810

Gnomad4 AFR exome AF: 0.675

Gnomad4 AMR exome AF: 0.766

Gnomad4 ASJ exome AF: 0.616

Gnomad4 EAS exome AF: 0.820

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.545

Gnomad4 NFE exome AF: 0.547

Gnomad4 OTH exome AF: 0.584

GnomAD4 genome AF: 0.610 AC: 92692 AN: 151990 Hom.: 28639 Cov.: 32 AF XY: 0.611 AC XY: 45367 AN XY: 74288

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.615

Alfa AF: 0.514 Hom.: 2704

Bravo AF: 0.625

Asia WGS AF: 0.711 AC: 2474 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 11, 2019

- -

Cone dystrophy with supernormal rod response Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.012
Dann	Benign	0.44

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: rs7029012; hg19: chr9-2717698; COSMIC: COSV66056364; COSMIC: COSV66056364;