9-2729475-C-T

Position:

chr9-2729475-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_133497.4(KCNV2):c.1386C>T(p.Asp462=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0703 in 1,613,786 control chromosomes in the GnomAD database, including 4,479 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 388 hom., cov: 32)

Exomes 𝑓: 0.071 ( 4091 hom. )

Consequence

KCNV2
NM_133497.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.07

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:

PUM3 (HGNC:29676): (pumilio RNA binding family member 3) Enables RNA binding activity. Involved in regulation of protein ADP-ribosylation. Located in chromosome; endoplasmic reticulum; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

PUM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 9-2729475-C-T is Benign according to our data. Variant chr9-2729475-C-T is described in ClinVar as [Benign]. Clinvar id is 262359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-2729475-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0925 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.1386C>T	p.Asp462=	synonymous_variant	2/2	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.1386C>T	p.Asp462=	synonymous_variant	2/2	1	NM_133497.4	ENSP00000371514	P1
PUM3	ENST00000490444.2 linkuse as main transcript	c.*127-8943G>A		intron_variant, NMD_transcript_variant		5		ENSP00000474467

Frequencies

GnomAD3 genomes

AF:

0.0631

AC:

9606

AN:

152134

Hom.:

390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0965

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.0243

Gnomad SAS

AF:

0.0460

Gnomad FIN

AF:

0.0703

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0740

Gnomad OTH

AF:

0.0646

GnomAD3 exomes

AF:

0.0745

AC:

18738

AN:

251370

Hom.:

897

AF XY:

0.0705

AC XY:

9584

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.0338

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.0241

Gnomad SAS exome

AF:

0.0466

Gnomad FIN exome

AF:

0.0742

Gnomad NFE exome

AF:

0.0724

Gnomad OTH exome

AF:

0.0736

GnomAD4 exome

AF:

0.0710

AC:

103778

AN:

1461534

Hom.:

4091

Cov.:

AF XY:

0.0697

AC XY:

50692

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.0325

Gnomad4 AMR exome

AF:

0.137

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.0215

Gnomad4 SAS exome

AF:

0.0458

Gnomad4 FIN exome

AF:

0.0768

Gnomad4 NFE exome

AF:

0.0726

Gnomad4 OTH exome

AF:

0.0680

GnomAD4 genome

AF:

0.0631

AC:

9604

AN:

152252

Hom.:

388

Cov.:

AF XY:

0.0620

AC XY:

4618

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0339

Gnomad4 AMR

AF:

0.0966

Gnomad4 ASJ

AF:

0.110

Gnomad4 EAS

AF:

0.0241

Gnomad4 SAS

AF:

0.0461

Gnomad4 FIN

AF:

0.0703

Gnomad4 NFE

AF:

0.0740

Gnomad4 OTH

AF:

0.0625

Alfa

AF:

0.0733

Hom.:

242

Bravo

AF:

0.0647

Asia WGS

AF:

0.0360

AC:

127

AN:

3478

EpiCase

AF:

0.0694

EpiControl

AF:

0.0634

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cone dystrophy with supernormal rod response

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

-0.28

CADD

Benign

9.6

DANN

Benign

0.82

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