rs10967705

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_133497.4(KCNV2):c.183C>G(p.Gly61Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 1,613,780 control chromosomes in the GnomAD database, including 273,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G61G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.60 ( 27919 hom., cov: 32)

Exomes 𝑓: 0.58 ( 245592 hom. )

Consequence

KCNV2
NM_133497.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -9.44

Publications

27 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 9-2717922-C-G is Benign according to our data. Variant chr9-2717922-C-G is described in ClinVar as Benign. ClinVar VariationId is 96357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-9.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNV2	NM_133497.4	MANE Select	c.183C>G	p.Gly61Gly	synonymous	Exon 1 of 2	NP_598004.1	Q8TDN2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNV2	ENST00000382082.4	TSL:1 MANE Select	c.183C>G	p.Gly61Gly	synonymous	Exon 1 of 2	ENSP00000371514.3	Q8TDN2
ENSG00000286670	ENST00000768783.1		n.113+28376G>C		intron	N/A
ENSG00000286670	ENST00000768784.1		n.156+14023G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91541

AN:

151872

Hom.:

27888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.631

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.614

Gnomad EAS

AF:

0.790

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.540

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.561

Gnomad OTH

AF:

0.614

GnomAD2 exomes

AF:

0.618

AC:

155283

AN:

251212

AF XY:

0.609

show subpopulations

Gnomad AFR exome

AF:

0.635

Gnomad AMR exome

AF:

0.783

Gnomad ASJ exome

AF:

0.610

Gnomad EAS exome

AF:

0.781

Gnomad FIN exome

AF:

0.534

Gnomad NFE exome

AF:

0.558

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.576

AC:

842285

AN:

1461790

Hom.:

245592

Cov.:

AF XY:

0.576

AC XY:

418852

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.638

AC:

21352

AN:

33480

American (AMR)

AF:

0.772

AC:

34544

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

15960

AN:

26132

East Asian (EAS)

AF:

0.809

AC:

32100

AN:

39698

South Asian (SAS)

AF:

0.615

AC:

53011

AN:

86252

European-Finnish (FIN)

AF:

0.535

AC:

28567

AN:

53416

Middle Eastern (MID)

AF:

0.577

AC:

3328

AN:

5768

European-Non Finnish (NFE)

AF:

0.556

AC:

618108

AN:

1111928

Other (OTH)

AF:

0.585

AC:

35315

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

23986

47972

71957

95943

119929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17538

35076

52614

70152

87690

<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:

0.603

AC:

91620

AN:

151990

Hom.:

27919

Cov.:

AF XY:

0.604

AC XY:

44851

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.631

AC:

26161

AN:

41452

American (AMR)

AF:

0.687

AC:

10498

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

2129

AN:

3466

East Asian (EAS)

AF:

0.791

AC:

4069

AN:

5144

South Asian (SAS)

AF:

0.624

AC:

3001

AN:

4812

European-Finnish (FIN)

AF:

0.540

AC:

5720

AN:

10584

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.561

AC:

38082

AN:

67940

Other (OTH)

AF:

0.617

AC:

1301

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1860

3720

5581

7441

9301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.578

Hom.:

8271

Bravo

AF:

0.618

EpiCase

AF:

0.556

EpiControl

AF:

0.563

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Cone dystrophy with supernormal rod response (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.029

(source)

DANN

Benign

0.57

PhyloP100

-9.4

PromoterAI

-0.020

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over