rs7859993

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_133497.4(KCNV2):c.915G>A(p.Val305Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 1,613,348 control chromosomes in the GnomAD database, including 1,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 159 hom., cov: 33)

Exomes 𝑓: 0.047 ( 1817 hom. )

Consequence

KCNV2
NM_133497.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.345

Publications

5 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=0.031).

BP6

Variant 9-2718654-G-A is Benign according to our data. Variant chr9-2718654-G-A is described in ClinVar as Benign. ClinVar VariationId is 262363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.345 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNV2	NM_133497.4 link	c.915G>A	p.Val305Val	synonymous_variant	Exon 1 of 2	ENST00000382082.4	NP_598004.1	Q8TDN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNV2	ENST00000382082.4 link	c.915G>A	p.Val305Val	synonymous_variant	Exon 1 of 2	1	NM_133497.4	ENSP00000371514.3	Q8TDN2
ENSG00000286670	ENST00000768783.1 link	n.113+27644C>T		intron_variant	Intron 1 of 3
ENSG00000286670	ENST00000768784.1 link	n.156+13291C>T		intron_variant	Intron 1 of 3
ENSG00000286670	ENST00000768785.1 link	n.156+13291C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0429

AC:

6535

AN:

152194

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0423

Gnomad AMI

AF:

0.0804

Gnomad AMR

AF:

0.0336

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.0303

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0536

Gnomad OTH

AF:

0.0320

GnomAD2 exomes

AF:

0.0353

AC:

8802

AN:

249330

AF XY:

0.0346

show subpopulations

Gnomad AFR exome

AF:

0.0421

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.0301

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0314

Gnomad NFE exome

AF:

0.0520

Gnomad OTH exome

AF:

0.0334

GnomAD4 exome

AF:

0.0470

AC:

68719

AN:

1461036

Hom.:

1817

Cov.:

AF XY:

0.0459

AC XY:

33388

AN XY:

726876

show subpopulations

African (AFR)

AF:

0.0425

AC:

1423

AN:

33470

American (AMR)

AF:

0.0221

AC:

989

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0310

AC:

811

AN:

26122

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39692

South Asian (SAS)

AF:

0.0129

AC:

1117

AN:

86256

European-Finnish (FIN)

AF:

0.0331

AC:

1748

AN:

52786

Middle Eastern (MID)

AF:

0.00520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0541

AC:

60157

AN:

1111852

Other (OTH)

AF:

0.0404

AC:

2442

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

4526

9052

13577

18103

22629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2186

4372

6558

8744

10930

<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:

0.0429

AC:

6538

AN:

152312

Hom.:

159

Cov.:

AF XY:

0.0404

AC XY:

3009

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0422

AC:

1756

AN:

41584

American (AMR)

AF:

0.0336

AC:

514

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0305

AC:

106

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5160

South Asian (SAS)

AF:

0.0114

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0303

AC:

322

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0536

AC:

3644

AN:

68020

Other (OTH)

AF:

0.0317

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

341

682

1022

1363

1704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0489

Hom.:

535

Bravo

AF:

0.0434

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cone dystrophy with supernormal rod response

Benign:1

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.9

(source)

DANN

Benign

0.89

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over