Variant 9-2717676-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr9-2717676-T-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
KCNV2	NM_133497.4 linkuse as main transcript	c.-64T>G		5_prime_UTR_variant	1/2	ENST00000382082.4	NP_598004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNV2	ENST00000382082.4 linkuse as main transcript	c.-64T>G		5_prime_UTR_variant	1/2	1	NM_133497.4	ENSP00000371514	P1

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

Gnomad4 AFR exome

AF:

0.0658

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.333

Gnomad4 EAS exome

AF:

0.258

Gnomad4 SAS exome

AF:

0.366

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.220

GnomAD4 genome

AF:

0.174

AC:

26522

AN:

152130

Hom.:

2718

Cov.:

AF XY:

0.177

AC XY:

13177

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0707

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.242

Gnomad4 SAS

AF:

0.360

Gnomad4 FIN

AF:

0.208

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.206

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cone dystrophy with supernormal rod response

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

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

DANN

Benign

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over