2-154698683-T-TCCCCCCCCCCCC

Variant names:

• chr2-154698683-T-TCCCCCCCCCCCC
• rs5835535
• ENST00000544049.2:c.-88_-87insCCCCCCCCCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000544049.2(KCNJ3):​c.-88_-87insCCCCCCCCCCCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: KCNJ3 ENST00000544049.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.896
• Publications: 0 publications found

Genes affected

KCNJ3 (HGNC:6264): (potassium inwardly rectifying channel subfamily J member 3) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and plays an important role in regulating heartbeat. It associates with three other G-protein-activated potassium channels to form a heteromultimeric pore-forming complex that also couples to neurotransmitter receptors in the brain and whereby channel activation can inhibit action potential firing by hyperpolarizing the plasma membrane. These multimeric G-protein-gated inwardly-rectifying potassium (GIRK) channels may play a role in the pathophysiology of epilepsy, addiction, Down's syndrome, ataxia, and Parkinson's disease. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, May 2012]

ENSG00000287900 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000544049.2. 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
	KCNJ3	NM_002239.4	MANE Select	c.-93_-92insCCCCCCCCCCCC		upstream_gene	N/A	NP_002230.1	P48549-1
	KCNJ3	NM_001260509.2		c.-93_-92insCCCCCCCCCCCC		upstream_gene	N/A	NP_001247438.1	D2X9V0
	KCNJ3	NM_001260510.2		c.-93_-92insCCCCCCCCCCCC		upstream_gene	N/A	NP_001247439.1	D2XBF0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ3	ENST00000544049.2	TSL:1	c.-88_-87insCCCCCCCCCCCC		5_prime_UTR	Exon 1 of 2	ENSP00000438410.1	P48549-2
	KCNJ3	ENST00000651198.1		c.-42-583_-42-582insCCCCCCCCCCCC		intron	N/A	ENSP00000498639.1	A0A494C0M7
	ENSG00000287900	ENST00000803267.1		n.769_770insGGGGGGGGGGGG		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000278 AC: 2 AN: 71950 Hom.: 0 Cov.: 2 AF XY: 0.0000510 AC XY: 2 AN XY: 39228

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 3144

American (AMR) AF: 0.00 AC: 0 AN: 5732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 812

East Asian (EAS) AF: 0.00 AC: 0 AN: 4884

South Asian (SAS) AF: 0.000122 AC: 1 AN: 8164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1268

European-Non Finnish (NFE) AF: 0.0000327 AC: 1 AN: 30548

Other (OTH) AF: 0.00 AC: 0 AN: 2694

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.90

Splicing

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

Other links and lift over

dbSNP: rs5835535; hg19: chr2-155555195;