rs12237048

Variant names:

• chr9-2718534-C-G
• rs12237048
• NM_133497.4:c.795C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-2718534-C-G
• chr9-2718534-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_133497.4(KCNV2):​c.795C>G​(p.Ala265Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,610,066 control chromosomes in the GnomAD database, including 179,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (16274 hom., cov: 34)
  • Exomes 𝑓: 0.47 (163548 hom.)
• Consequence: KCNV2 NM_133497.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.744
• Publications: 19 publications found

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

ENSG00000286670 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 9-2718534-C-G is Benign according to our data. Variant chr9-2718534-C-G is described in ClinVar as Benign. ClinVar VariationId is 96362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.744 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 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.795C>G	p.Ala265Ala	synonymous	Exon 1 of 2	NP_598004.1	Q8TDN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNV2	ENST00000382082.4	TSL:1 MANE Select	c.795C>G	p.Ala265Ala	synonymous	Exon 1 of 2	ENSP00000371514.3	Q8TDN2
	ENSG00000286670	ENST00000768783.1		n.113+27764G>C		intron	N/A
	ENSG00000286670	ENST00000768784.1		n.156+13411G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.454 AC: 69022 AN: 152012 Hom.: 16253 Cov.: 34

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.459

GnomAD2 exomes AF: 0.484 AC: 115469 AN: 238632 AF XY: 0.475

Gnomad AFR exome AF: 0.374

Gnomad AMR exome AF: 0.565

Gnomad ASJ exome AF: 0.458

Gnomad EAS exome AF: 0.717

Gnomad FIN exome AF: 0.521

Gnomad NFE exome AF: 0.463

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.469 AC: 684264 AN: 1457936 Hom.: 163548 Cov.: 67 AF XY: 0.466 AC XY: 337951 AN XY: 725032

African (AFR) AF: 0.372 AC: 12430 AN: 33450

American (AMR) AF: 0.564 AC: 24981 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 11993 AN: 26032

East Asian (EAS) AF: 0.731 AC: 28935 AN: 39572

South Asian (SAS) AF: 0.371 AC: 31837 AN: 85920

European-Finnish (FIN) AF: 0.513 AC: 26755 AN: 52132

Middle Eastern (MID) AF: 0.429 AC: 2470 AN: 5752

European-Non Finnish (NFE) AF: 0.465 AC: 516433 AN: 1110552

Other (OTH) AF: 0.472 AC: 28430 AN: 60234

GnomAD4 genome AF: 0.454 AC: 69054 AN: 152130 Hom.: 16274 Cov.: 34 AF XY: 0.457 AC XY: 34029 AN XY: 74400

African (AFR) AF: 0.372 AC: 15455 AN: 41522

American (AMR) AF: 0.513 AC: 7849 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1626 AN: 3468

East Asian (EAS) AF: 0.727 AC: 3731 AN: 5134

South Asian (SAS) AF: 0.387 AC: 1872 AN: 4832

European-Finnish (FIN) AF: 0.522 AC: 5536 AN: 10596

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31527 AN: 67960

Other (OTH) AF: 0.465 AC: 983 AN: 2114

Alfa AF: 0.414 Hom.: 3915

Bravo AF: 0.455

Asia WGS AF: 0.541 AC: 1878 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Cone dystrophy with supernormal rod response (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.1
DANN	Benign	0.82
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12237048; hg19: chr9-2718534; COSMIC: COSV66056316; COSMIC: COSV66056316;