chr7-120273436-A-C

Variant names:

• chr7-120273436-A-C
• rs181685823
• NM_012281.3:c.-1197A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

KCND2 Gene-Disease associations (from GenCC):

• KCND2-related neurodevelopmental disorder with or without seizures

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

ENSG00000309549 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012281.3. 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
	KCND2	NM_012281.3	MANE Select	c.-1197A>C		5_prime_UTR	Exon 1 of 6	NP_036413.1	Q9NZV8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCND2	ENST00000331113.9	TSL:1 MANE Select	c.-1197A>C		5_prime_UTR	Exon 1 of 6	ENSP00000333496.4	Q9NZV8
	ENSG00000309549	ENST00000841943.1		n.91+91T>G		intron	N/A
	ENSG00000309549	ENST00000841944.1		n.91+91T>G		intron	N/A

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

African (AFR) AF: 0.170 AC: 6823 AN: 40226

American (AMR) AF: 0.172 AC: 2530 AN: 14682

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 688 AN: 3410

East Asian (EAS) AF: 0.0993 AC: 483 AN: 4862

South Asian (SAS) AF: 0.0694 AC: 310 AN: 4468

European-Finnish (FIN) AF: 0.0906 AC: 753 AN: 8314

Middle Eastern (MID) AF: 0.145 AC: 41 AN: 282

European-Non Finnish (NFE) AF: 0.160 AC: 10530 AN: 65782

Other (OTH) AF: 0.169 AC: 344 AN: 2032

Alfa AF: 0.0519 Hom.: 49

Bravo AF: 0.163

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.77
DANN	Benign	0.46
PhyloP100		-0.83
PromoterAI		0.0068	Neutral

Splicing

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

Other links and lift over

dbSNP: rs181685823; hg19: chr7-119913490;