rs2836055

Variant names:

• chr21-37925512-T-C
• rs2836055
• ENST00000645093.1:c.-27-84803A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000645093.1(KCNJ6):​c.-27-84803A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,200 control chromosomes in the GnomAD database, including 5,474 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 0.20 (5474 hom., cov: 32)
• Consequence: KCNJ6 ENST00000645093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 1 publications found

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]

KCNJ6 Gene-Disease associations (from GenCC):

• Keppen-Lubinsky syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000645093.1	c.-27-84803A>G		intron_variant	Intron 2 of 4			ENSP00000493772.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30938 AN: 152082 Hom.: 5464 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.203 AC: 30972 AN: 152200 Hom.: 5474 Cov.: 32 AF XY: 0.194 AC XY: 14454 AN XY: 74434

African (AFR) AF: 0.489 AC: 20276 AN: 41448

American (AMR) AF: 0.115 AC: 1763 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 332 AN: 3470

East Asian (EAS) AF: 0.0544 AC: 282 AN: 5180

South Asian (SAS) AF: 0.0760 AC: 367 AN: 4828

European-Finnish (FIN) AF: 0.0374 AC: 397 AN: 10626

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7073 AN: 68022

Other (OTH) AF: 0.174 AC: 369 AN: 2116

Alfa AF: 0.148 Hom.: 6065

Bravo AF: 0.222

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs2836055; hg19: chr21-39297815;