9-2718822-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_133497.4(KCNV2):c.1083A>G(p.Gln361Gln) 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

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.518

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

cone dystrophy with supernormal rod response
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
inherited retinal dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

KCNV2 links:

ENSG00000286670 (HGNC:):

ENSG00000286670 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.074).

BP6

Variant 9-2718822-A-G is Benign according to our data. Variant chr9-2718822-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 96356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133497.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNV2	NM_133497.4	MANE Select	c.1083A>G	p.Gln361Gln	synonymous	Exon 1 of 2	NP_598004.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KCNV2	ENST00000382082.4	TSL:1 MANE Select	c.1083A>G	p.Gln361Gln	synonymous	Exon 1 of 2	ENSP00000371514.3
ENSG00000286670	ENST00000768783.1		n.113+27476T>C		intron	N/A
ENSG00000286670	ENST00000768784.1		n.156+13123T>C		intron	N/A

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

GnomAD2 exomes

AF:

0.00842

AC:

2082

AN:

247350

AF XY:

0.00850

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 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

African (AFR)

AF:

0.00149

AC:

AN:

33474

American (AMR)

AF:

0.00814

AC:

364

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0265

AC:

693

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00281

AC:

242

AN:

86252

European-Finnish (FIN)

AF:

0.00878

AC:

433

AN:

49306

Middle Eastern (MID)

AF:

0.0201

AC:

116

AN:

5768

European-Non Finnish (NFE)

AF:

0.0105

AC:

11645

AN:

1111878

Other (OTH)

AF:

0.00969

AC:

585

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1078

2156

3233

4311

5389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

460

920

1380

1840

2300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00708

AC:

1078

AN:

152350

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

510

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00151

AC:

AN:

41588

American (AMR)

AF:

0.00719

AC:

110

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

101

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00186

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00941

AC:

100

AN:

10626

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00975

AC:

663

AN:

68026

Other (OTH)

AF:

0.00993

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

121

181

242

302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00982

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KCNV2: BP4, BP7, BS1, BS2

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

Sep 20, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Cone dystrophy with supernormal rod response

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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.

Sep 29, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.0

(source)

DANN

Benign

0.36

PhyloP100

0.52

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over