rs7860945

Positions:

chr9-2718717-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_133497.4(KCNV2):c.978C>T(p.Asp326=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 1,613,088 control chromosomes in the GnomAD database, including 1,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 196 hom., cov: 33)

Exomes 𝑓: 0.042 ( 1403 hom. )

Consequence

KCNV2
NM_133497.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.365

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 9-2718717-C-T is Benign according to our data. Variant chr9-2718717-C-T is described in ClinVar as [Benign]. Clinvar id is 262364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.365 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0608 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.978C>T	p.Asp326=	synonymous_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.978C>T	p.Asp326=	synonymous_variant	1/2	1	NM_133497.4	ENSP00000371514	P1

Frequencies

GnomAD3 genomes

AF:

0.0460

AC:

6999

AN:

152228

Hom.:

196

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0629

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.0302

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0105

Gnomad FIN

AF:

0.0291

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0478

Gnomad OTH

AF:

0.0363

GnomAD3 exomes

AF:

0.0344

AC:

8584

AN:

249466

Hom.:

209

AF XY:

0.0331

AC XY:

4475

AN XY:

135306

show subpopulations

Gnomad AFR exome

AF:

0.0647

Gnomad AMR exome

AF:

0.0213

Gnomad ASJ exome

AF:

0.0300

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0118

Gnomad FIN exome

AF:

0.0301

Gnomad NFE exome

AF:

0.0472

Gnomad OTH exome

AF:

0.0306

GnomAD4 exome

AF:

0.0417

AC:

60972

AN:

1460742

Hom.:

1403

Cov.:

AF XY:

0.0408

AC XY:

29655

AN XY:

726764

show subpopulations

Gnomad4 AFR exome

AF:

0.0632

Gnomad4 AMR exome

AF:

0.0230

Gnomad4 ASJ exome

AF:

0.0306

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0120

Gnomad4 FIN exome

AF:

0.0314

Gnomad4 NFE exome

AF:

0.0468

Gnomad4 OTH exome

AF:

0.0372

GnomAD4 genome

AF:

0.0460

AC:

7004

AN:

152346

Hom.:

196

Cov.:

AF XY:

0.0432

AC XY:

3216

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0628

Gnomad4 AMR

AF:

0.0344

Gnomad4 ASJ

AF:

0.0302

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0291

Gnomad4 NFE

AF:

0.0478

Gnomad4 OTH

AF:

0.0360

Alfa

AF:

0.0465

Hom.:

129

Bravo

AF:

0.0478

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0415

EpiControl

AF:

0.0435

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

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

-0.54

CADD

Benign

6.4

DANN

Benign

0.93

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