9-2717922-C-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.183C>G(p.Gly61=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 1,613,780 control chromosomes in the GnomAD database, including 273,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G61G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.60 (27919 hom., cov: 32)
  • Exomes 𝑓: 0.58 (245592 hom.)
• Consequence: KCNV2 NM_133497.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -9.44

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=-0.93).
• BP6: Variant 9-2717922-C-G is Benign according to our data. Variant chr9-2717922-C-G is described in ClinVar as [Benign]. Clinvar id is 96357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-2717922-C-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-9.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNV2	NM_133497.4	c.183C>G	p.Gly61=	synonymous_variant	1/2	ENST00000382082.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNV2	ENST00000382082.4	c.183C>G	p.Gly61=	synonymous_variant	1/2	1	NM_133497.4	P1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91541 AN: 151872 Hom.: 27888 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.614

GnomAD3 exomes AF: 0.618 AC: 155283 AN: 251212 Hom.: 49137 AF XY: 0.609 AC XY: 82637 AN XY: 135772

Gnomad AFR exome AF: 0.635

Gnomad AMR exome AF: 0.783

Gnomad ASJ exome AF: 0.610

Gnomad EAS exome AF: 0.781

Gnomad SAS exome AF: 0.616

Gnomad FIN exome AF: 0.534

Gnomad NFE exome AF: 0.558

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.576 AC: 842285 AN: 1461790 Hom.: 245592 Cov.: 67 AF XY: 0.576 AC XY: 418852 AN XY: 727182

Gnomad4 AFR exome AF: 0.638

Gnomad4 AMR exome AF: 0.772

Gnomad4 ASJ exome AF: 0.611

Gnomad4 EAS exome AF: 0.809

Gnomad4 SAS exome AF: 0.615

Gnomad4 FIN exome AF: 0.535

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.585

GnomAD4 genome AF: 0.603 AC: 91620 AN: 151990 Hom.: 27919 Cov.: 32 AF XY: 0.604 AC XY: 44851 AN XY: 74286

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.791

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.617

Alfa AF: 0.578 Hom.: 8271

Bravo AF: 0.618

EpiCase AF: 0.556

EpiControl AF: 0.563

ClinVar

Significance: Benign

Submissions summary: Benign:6

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)	Jun 10, 2014	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2020	- -

Cone dystrophy with supernormal rod response Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
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	-0.93
Cadd	Benign	0.029
Dann	Benign	0.57

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: rs10967705; hg19: chr9-2717922; COSMIC: COSV66055463; COSMIC: COSV66055463;