rs2835936

chr21-37753879-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002240.5(KCNJ6):c.26-38748G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,148 control chromosomes in the GnomAD database, including 4,127 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4127 hom., cov: 32)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

Genes affected

KCNJ6 (HGNC:6267): (potassium inwardly rectifying channel subfamily J member 6) This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability. [provided by RefSeq, Apr 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ6	NM_002240.5	c.26-38748G>A		intron_variant		ENST00000609713.2
LOC101928368	XR_244309.5	n.81-691C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ6	ENST00000609713.2	c.26-38748G>A		intron_variant		1	NM_002240.5	P1
	ENST00000711631.1	n.71-691C>T		intron_variant, non_coding_transcript_variant
KCNJ6	ENST00000645093.1	c.26-38748G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32562 AN: 152030 Hom.: 4124 Cov.: 32

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.214 AC: 32565 AN: 152148 Hom.: 4127 Cov.: 32 AF XY: 0.214 AC XY: 15929 AN XY: 74390

Gnomad4 AFR AF: 0.0783

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.247

Alfa AF: 0.250 Hom.: 2827

Bravo AF: 0.210

Asia WGS AF: 0.231 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.9
Dann	Benign	0.61

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

Other links and lift over

dbSNP: rs2835936; hg19: chr21-39126182;