7-120273436-A-C

Position:

• chr7-120273436-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012281.3(KCND2):​c.-1197A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 144,946 control chromosomes in the GnomAD database, including 1,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (1813 hom., cov: 31)
• Consequence: KCND2 NM_012281.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.835

Genes affected

KCND2 (HGNC:6238): (potassium voltage-gated channel subfamily D 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. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member mediates a rapidly inactivating, A-type outward potassium current which is not under the control of the N terminus as it is in Shaker channels. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-120273436-A-C is Benign according to our data. Variant chr7-120273436-A-C is described in ClinVar as [Benign]. Clinvar id is 1283256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND2	NM_012281.3	c.-1197A>C		5_prime_UTR_variant	1/6	ENST00000331113.9	NP_036413.1
KCND2	XM_047420346.1	c.-1197A>C		5_prime_UTR_variant	2/7		XP_047276302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCND2	ENST00000331113	c.-1197A>C		5_prime_UTR_variant	1/6	1	NM_012281.3	ENSP00000333496.4

Frequencies

GnomAD3 genomes AF: 0.157 AC: 22689 AN: 144878 Hom.: 1813 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.154

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.157 AC: 22688 AN: 144946 Hom.: 1813 Cov.: 31 AF XY: 0.149 AC XY: 10528 AN XY: 70528

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.0993

Gnomad4 SAS AF: 0.0694

Gnomad4 FIN AF: 0.0906

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.169

Alfa AF: 0.0519 Hom.: 49

Bravo AF: 0.163

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.77
DANN	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs181685823; hg19: chr7-119913490;