rs142744007

Positions:

chr9-2718822-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000382082.4(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
ENST00000382082.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.518

Variant links:

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]

KCNV2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNV2	NM_133497.4 linkuse as main transcript	c.1083A>G	p.Gln361=	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 linkuse as main transcript	c.1083A>G	p.Gln361=	synonymous_variant	1/2	1	NM_133497.4	ENSP00000371514	P1

Frequencies

GnomAD3 genomes

AF:

0.00709

AC:

1080

AN:

152232

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00850

AC XY:

1142

AN XY:

134308

show subpopulations

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.:

Cov.:

AF XY:

0.00964

AC XY:

6994

AN XY:

725368

show subpopulations

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.:

Cov.:

AF XY:

0.00685

AC XY:

510

AN XY:

74504

show subpopulations

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.:

Bravo

AF:

0.00714

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0126

EpiControl

AF:

0.0125

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	KCNV2: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

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	-	- -

Cone dystrophy with supernormal rod response

Benign:2

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

-0.92

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over