rs142744007

chr9-2718822-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_133497.4(KCNV2):c.1083A>G(p.Gln361=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00945 in 1,609,906 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0071 (9 hom., cov: 33)
  • Exomes 𝑓: 0.0097 (81 hom.)
• Consequence: KCNV2 NM_133497.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.518

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=-0.92).
• BP6: Variant 9-2718822-A-G is Benign according to our data. Variant chr9-2718822-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 96356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-2718822-A-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.518 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00708 (1078/152350) while in subpopulation NFE AF= 0.00975 (663/68026). AF 95% confidence interval is 0.00913. There are 9 homozygotes in gnomad4. There are 510 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNV2	NM_133497.4	c.1083A>G	p.Gln361=	synonymous_variant	1/2	ENST00000382082.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNV2	ENST00000382082.4	c.1083A>G	p.Gln361=	synonymous_variant	1/2	1	NM_133497.4	P1

Frequencies

GnomAD3 genomes AF: 0.00709 AC: 1080 AN: 152232 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00941

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00975

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00842 AC: 2082 AN: 247350 Hom.: 18 AF XY: 0.00850 AC XY: 1142 AN XY: 134308

Gnomad AFR exome AF: 0.000930

Gnomad AMR exome AF: 0.00770

Gnomad ASJ exome AF: 0.0267

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00271

Gnomad FIN exome AF: 0.00979

Gnomad NFE exome AF: 0.0105

Gnomad OTH exome AF: 0.0133

GnomAD4 exome AF: 0.00969 AC: 14128 AN: 1457556 Hom.: 81 Cov.: 36 AF XY: 0.00964 AC XY: 6994 AN XY: 725368

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00814

Gnomad4 ASJ exome AF: 0.0265

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00281

Gnomad4 FIN exome AF: 0.00878

Gnomad4 NFE exome AF: 0.0105

Gnomad4 OTH exome AF: 0.00969

GnomAD4 genome AF: 0.00708 AC: 1078 AN: 152350 Hom.: 9 Cov.: 33 AF XY: 0.00685 AC XY: 510 AN XY: 74504

Gnomad4 AFR AF: 0.00151

Gnomad4 AMR AF: 0.00719

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00941

Gnomad4 NFE AF: 0.00975

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.0107 Hom.: 3

Bravo AF: 0.00714

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0126

EpiControl AF: 0.0125

ClinVar

Significance: Benign/Likely 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	Eurofins Ntd Llc (ga)	Sep 20, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2022	KCNV2: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -

Cone dystrophy with supernormal rod response Benign:2

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. -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Sep 29, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.0
Dann	Benign	0.36

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: rs142744007; hg19: chr9-2718822; COSMIC: COSV66055704; COSMIC: COSV66055704;