rs77818131

chr2-232771149-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002242.4(KCNJ13):c.214G>T(p.Ala72Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNJ13 NM_002242.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

Genes affected

KCNJ13 (HGNC:6259): (potassium inwardly rectifying channel subfamily J member 13) This gene encodes a member of the inwardly rectifying potassium channel family of proteins. Members of this family form ion channel pores that allow potassium ions to pass into a cell. The encoded protein belongs to a subfamily of low signal channel conductance proteins that have a low dependence on potassium concentration. Mutations in this gene are associated with snowflake vitreoretinal degeneration. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2010]

GIGYF2 (HGNC:11960): (GRB10 interacting GYF protein 2) This gene contains CAG trinucleotide repeats and encodes a protein containing several stretches of polyglutamine residues. The encoded protein may be involved in the regulation of tyrosine kinase receptor signaling. This gene is located in a chromosomal region that was genetically linked to Parkinson disease type 11, and mutations in this gene were thought to be causative for this disease. However, more recent studies in different populations have been unable to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ13	NM_002242.4	c.214G>T	p.Ala72Ser	missense_variant	2/3	ENST00000233826.4
GIGYF2	NM_001103146.3	c.532+9713C>A		intron_variant		ENST00000373563.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ13	ENST00000233826.4	c.214G>T	p.Ala72Ser	missense_variant	2/3	1	NM_002242.4	P1
GIGYF2	ENST00000373563.9	c.532+9713C>A		intron_variant		1	NM_001103146.3	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000741 AC: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.36
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.41	T;.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.3	M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Uncertain	0.45
Sift	Uncertain	0.015	D;D;D
Sift4G	Benign	0.20	T;D;T
Polyphen		1.0	D;.;D
Vest4		0.80
MutPred		0.74		Gain of MoRF binding (P = 0.2168);Gain of MoRF binding (P = 0.2168);Gain of MoRF binding (P = 0.2168);
MVP		0.37
MPC		1.4
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.72
gMVP		0.98

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: rs77818131; hg19: chr2-233635859; COSMIC: COSV52086248; COSMIC: COSV52086248;