9-2717676-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_133497.4(KCNV2):c.-64T>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 0.212 in 1,604,192 control chromosomes in the GnomAD database, including 38,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2718 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36044 hom. )

Consequence

KCNV2
NM_133497.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0490

Publications

11 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 9-2717676-T-G is Benign according to our data. Variant chr9-2717676-T-G is described in ClinVar as [Benign]. Clinvar id is 366402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNV2	NM_133497.4 link	c.-64T>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.-64T>G	5_prime_UTR_variant	Exon 1 of 2	1	NM_133497.4	ENSP00000371514.3	Q8TDN2
ENSG00000286670	ENST00000768783.1 link	n.113+28622A>C	intron_variant	Intron 1 of 3
ENSG00000286670	ENST00000768784.1 link	n.156+14269A>C	intron_variant	Intron 1 of 3
ENSG00000286670	ENST00000768785.1 link	n.156+14269A>C	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26531

AN:

152012

Hom.:

2720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0708

Gnomad AMI

AF:

0.239

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.360

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.205

GnomAD4 exome

AF:

0.215

AC:

312813

AN:

1452062

Hom.:

36044

Cov.:

AF XY:

0.221

AC XY:

160141

AN XY:

723068

show subpopulations

African (AFR)

AF:

0.0658

AC:

2192

AN:

33302

American (AMR)

AF:

0.145

AC:

6488

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

8680

AN:

26084

East Asian (EAS)

AF:

0.258

AC:

10238

AN:

39644

South Asian (SAS)

AF:

0.366

AC:

31319

AN:

85620

European-Finnish (FIN)

AF:

0.202

AC:

10627

AN:

52714

Middle Eastern (MID)

AF:

0.266

AC:

1521

AN:

5722

European-Non Finnish (NFE)

AF:

0.207

AC:

228502

AN:

1104216

Other (OTH)

AF:

0.220

AC:

13246

AN:

60082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

13271

26542

39814

53085

66356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.174

AC:

26522

AN:

152130

Hom.:

2718

Cov.:

AF XY:

0.177

AC XY:

13177

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0707

AC:

2938

AN:

41548

American (AMR)

AF:

0.155

AC:

2365

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1120

AN:

3468

East Asian (EAS)

AF:

0.242

AC:

1245

AN:

5154

South Asian (SAS)

AF:

0.360

AC:

1731

AN:

4810

European-Finnish (FIN)

AF:

0.208

AC:

2196

AN:

10578

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14192

AN:

67978

Other (OTH)

AF:

0.206

AC:

434

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1113

2225

3338

4450

5563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.200

Hom.:

652

Bravo

AF:

0.164

Asia WGS

AF:

0.288

AC:

1000

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Cone dystrophy with supernormal rod response

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.6

(source)

DANN

Benign

0.74

PhyloP100

-0.049

PromoterAI

-0.023

Neutral

(source)

Mutation Taster

=145/155

disease causing

(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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9-2717676-T-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