2-232768750-G-C

Position:

• chr2-232768750-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002242.4(KCNJ13):​c.524C>G​(p.Thr175Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T175I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNJ13 NM_002242.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16000995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ13	NM_002242.4	c.524C>G	p.Thr175Arg	missense_variant	3/3	ENST00000233826.4	NP_002233.2
GIGYF2	NM_001103146.3	c.532+7314G>C		intron_variant		ENST00000373563.9	NP_001096616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ13	ENST00000233826.4	c.524C>G	p.Thr175Arg	missense_variant	3/3	1	NM_002242.4	ENSP00000233826	P1
GIGYF2	ENST00000373563.9	c.532+7314G>C		intron_variant		1	NM_001103146.3	ENSP00000362664	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	11
DANN	Benign	0.60
DEOGEN2	Benign	0.19	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.14	.;T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.29	N;N;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.24	N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.35	T;T;T
Sift4G	Benign	0.39	T;T;.
Polyphen		0.0	B;B;.
Vest4		0.15
MutPred		0.51		Gain of MoRF binding (P = 0.0096);Gain of MoRF binding (P = 0.0096);.;
MVP		0.96
MPC		0.58
ClinPred		0.11	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1801251; hg19: chr2-233633460;