NM_002242.4:c.*1839A>G

Variant names:

• chr2-232766352-T-C
• rs34063802
• NM_002242.4:c.*1839A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002242.4(KCNJ13):​c.*1839A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 178,820 control chromosomes in the GnomAD database, including 3,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3002 hom., cov: 32)
  • Exomes 𝑓: 0.18 (554 hom.)
• Consequence: KCNJ13 NM_002242.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0300

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]

ENSG00000241409 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-232766352-T-C is Benign according to our data. Variant chr2-232766352-T-C is described in ClinVar as [Benign]. Clinvar id is 335032.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ13	NM_002242.4	c.*1839A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000233826.4	NP_002233.2
GIGYF2	NM_001103146.3	c.532+4916T>C		intron_variant	Intron 8 of 28	ENST00000373563.9	NP_001096616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ13	ENST00000233826	c.*1839A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_002242.4	ENSP00000233826.3
GIGYF2	ENST00000373563.9	c.532+4916T>C		intron_variant	Intron 8 of 28	1	NM_001103146.3	ENSP00000362664.5

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28955 AN: 152016 Hom.: 3007 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0934

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.180 AC: 4815 AN: 26686 Hom.: 554 AF XY: 0.173 AC XY: 2458 AN XY: 14238

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.0828

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.190 AC: 28961 AN: 152134 Hom.: 3002 Cov.: 32 AF XY: 0.191 AC XY: 14182 AN XY: 74372

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0922

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.215

Alfa AF: 0.179 Hom.: 681

Bravo AF: 0.185

Asia WGS AF: 0.113 AC: 396 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leber congenital amaurosis 16 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.76

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: rs34063802; hg19: chr2-233631062;