9-2717698-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_133497.4(KCNV2):c.-42C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,613,100 control chromosomes in the GnomAD database, including 270,065 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 28639 hom., cov: 32)

Exomes 𝑓: 0.57 ( 241426 hom. )

Consequence

KCNV2
NM_133497.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.40

Publications

17 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.12).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNV2	NM_133497.4 link	c.-42C>G		5_prime_UTR_variant	Exon 1 of 2	ENST00000382082.4	NP_598004.1	Q8TDN2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNV2	ENST00000382082.4 link	c.-42C>G	5_prime_UTR_variant	Exon 1 of 2	1	NM_133497.4	ENSP00000371514.3	Q8TDN2
ENSG00000286670	ENST00000768783.1 link	n.113+28600G>C	intron_variant	Intron 1 of 3
ENSG00000286670	ENST00000768784.1 link	n.156+14247G>C	intron_variant	Intron 1 of 3
ENSG00000286670	ENST00000768785.1 link	n.156+14247G>C	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.610

AC:

92594

AN:

151870

Hom.:

28599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.665

Gnomad AMI

AF:

0.547

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.806

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.548

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.555

Gnomad OTH

AF:

0.612

GnomAD2 exomes

AF:

0.619

AC:

154411

AN:

249504

AF XY:

0.609

show subpopulations

Gnomad AFR exome

AF:

0.669

Gnomad AMR exome

AF:

0.776

Gnomad ASJ exome

AF:

0.615

Gnomad EAS exome

AF:

0.795

Gnomad FIN exome

AF:

0.542

Gnomad NFE exome

AF:

0.551

Gnomad OTH exome

AF:

0.592

GnomAD4 exome

AF:

0.571

AC:

834291

AN:

1461110

Hom.:

241426

Cov.:

AF XY:

0.572

AC XY:

415388

AN XY:

726810

show subpopulations

African (AFR)

AF:

0.675

AC:

22596

AN:

33478

American (AMR)

AF:

0.766

AC:

34264

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.616

AC:

16101

AN:

26134

East Asian (EAS)

AF:

0.820

AC:

32562

AN:

39696

South Asian (SAS)

AF:

0.619

AC:

53277

AN:

86108

European-Finnish (FIN)

AF:

0.545

AC:

29006

AN:

53224

Middle Eastern (MID)

AF:

0.590

AC:

3401

AN:

5760

European-Non Finnish (NFE)

AF:

0.547

AC:

607799

AN:

1111620

Other (OTH)

AF:

0.584

AC:

35285

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

21175

42350

63526

84701

105876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.610

AC:

92692

AN:

151990

Hom.:

28639

Cov.:

AF XY:

0.611

AC XY:

45367

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.665

AC:

27561

AN:

41442

American (AMR)

AF:

0.679

AC:

10367

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

2146

AN:

3472

East Asian (EAS)

AF:

0.807

AC:

4153

AN:

5148

South Asian (SAS)

AF:

0.628

AC:

3020

AN:

4812

European-Finnish (FIN)

AF:

0.548

AC:

5799

AN:

10576

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.555

AC:

37687

AN:

67958

Other (OTH)

AF:

0.615

AC:

1297

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1863

3726

5589

7452

9315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.514

Hom.:

2704

Bravo

AF:

0.625

Asia WGS

AF:

0.711

AC:

2474

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 11, 2019

GeneDx

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

-1.1

CADD

Benign

0.012

(source)

DANN

Benign

0.44

PhyloP100

-3.4

PromoterAI

0.061

Neutral

(source)

Mutation Taster

=300/0

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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9-2717698-C-G

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