9-2718498-A-G

Position:

• chr9-2718498-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_133497.4(KCNV2):​c.759A>G​(p.Pro253=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,610,338 control chromosomes in the GnomAD database, including 8,982 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (852 hom., cov: 33)
  • Exomes 𝑓: 0.10 (8130 hom.)
• Consequence: KCNV2 NM_133497.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.31

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 9-2718498-A-G is Benign according to our data. Variant chr9-2718498-A-G is described in ClinVar as [Benign]. Clinvar id is 96361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-2718498-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNV2	NM_133497.4	c.759A>G	p.Pro253=	synonymous_variant	1/2	ENST00000382082.4	NP_598004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNV2	ENST00000382082.4	c.759A>G	p.Pro253=	synonymous_variant	1/2	1	NM_133497.4	ENSP00000371514	P1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15281 AN: 152068 Hom.: 853 Cov.: 33

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0253

Gnomad SAS AF: 0.0490

Gnomad FIN AF: 0.0797

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.102 AC: 24074 AN: 236654 Hom.: 1415 AF XY: 0.0970 AC XY: 12578 AN XY: 129624

Gnomad AFR exome AF: 0.0831

Gnomad AMR exome AF: 0.173

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.0260

Gnomad SAS exome AF: 0.0469

Gnomad FIN exome AF: 0.0807

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.102 AC: 148151 AN: 1458152 Hom.: 8130 Cov.: 80 AF XY: 0.0996 AC XY: 72233 AN XY: 725228

Gnomad4 AFR exome AF: 0.0819

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.0186

Gnomad4 SAS exome AF: 0.0472

Gnomad4 FIN exome AF: 0.0861

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.100 AC: 15283 AN: 152186 Hom.: 852 Cov.: 33 AF XY: 0.0992 AC XY: 7381 AN XY: 74428

Gnomad4 AFR AF: 0.0850

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0251

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.0797

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0974 Hom.: 321

Bravo AF: 0.105

Asia WGS AF: 0.0410 AC: 142 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 20, 2014	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Cone dystrophy with supernormal rod response Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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	-0.66
CADD	Benign	1.2
DANN	Benign	0.48

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: rs10967709; hg19: chr9-2718498;