chr9-2729475-C-T

Variant names:

• chr9-2729475-C-T
• rs41312842
• NM_133497.4:c.1386C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_133497.4(KCNV2):​c.1386C>T​(p.Asp462Asp) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.07
• Publications: 7 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]

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]

ENSG00000286670 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 262359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0925 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.1386C>T	p.Asp462Asp	synonymous	Exon 2 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.1386C>T	p.Asp462Asp	synonymous	Exon 2 of 2	ENSP00000371514.3	Q8TDN2
	PUM3	ENST00000490444.2	TSL:5	n.*127-8943G>A		intron	N/A	ENSP00000474467.1	S4R3K8
	ENSG00000286670	ENST00000768783.1		n.113+16823G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9606 AN: 152134 Hom.: 390 Cov.: 32

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

GnomAD2 exomes AF: 0.0745 AC: 18738 AN: 251370 AF XY: 0.0705

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 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.: 32 AF XY: 0.0697 AC XY: 50692 AN XY: 727080

African (AFR) AF: 0.0325 AC: 1086 AN: 33464

American (AMR) AF: 0.137 AC: 6108 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2746 AN: 26132

East Asian (EAS) AF: 0.0215 AC: 855 AN: 39700

South Asian (SAS) AF: 0.0458 AC: 3946 AN: 86240

European-Finnish (FIN) AF: 0.0768 AC: 4104 AN: 53420

Middle Eastern (MID) AF: 0.0262 AC: 148 AN: 5648

European-Non Finnish (NFE) AF: 0.0726 AC: 80682 AN: 1111830

Other (OTH) AF: 0.0680 AC: 4103 AN: 60380

GnomAD4 genome AF: 0.0631 AC: 9604 AN: 152252 Hom.: 388 Cov.: 32 AF XY: 0.0620 AC XY: 4618 AN XY: 74448

African (AFR) AF: 0.0339 AC: 1407 AN: 41552

American (AMR) AF: 0.0966 AC: 1478 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3468

East Asian (EAS) AF: 0.0241 AC: 125 AN: 5178

South Asian (SAS) AF: 0.0461 AC: 222 AN: 4820

European-Finnish (FIN) AF: 0.0703 AC: 745 AN: 10604

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0740 AC: 5036 AN: 68014

Other (OTH) AF: 0.0625 AC: 132 AN: 2112

Alfa AF: 0.0732 Hom.: 244

Bravo AF: 0.0647

Asia WGS AF: 0.0360 AC: 127 AN: 3478

EpiCase AF: 0.0694

EpiControl AF: 0.0634

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cone dystrophy with supernormal rod response (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	9.6
DANN	Benign	0.82
PhyloP100		4.1
Mutation Taster		=95/5	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: rs41312842; hg19: chr9-2729475; COSMIC: COSV66057551;