2-232765966-C-T

Position:

chr2-232765966-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002242.4(KCNJ13):c.*2225G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 466,168 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 100 hom., cov: 32)

Exomes 𝑓: 0.037 ( 292 hom. )

Consequence

KCNJ13
NM_002242.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0170

Variant links:

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]

KCNJ13 links:

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]

GIGYF2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 2-232765966-C-T is Benign according to our data. Variant chr2-232765966-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 898161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0326 (4806/147474) while in subpopulation NFE AF= 0.0493 (3265/66282). AF 95% confidence interval is 0.0478. There are 100 homozygotes in gnomad4. There are 2232 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 100 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ13	NM_002242.4 linkuse as main transcript	c.*2225G>A		3_prime_UTR_variant	3/3	ENST00000233826.4
GIGYF2	NM_001103146.3 linkuse as main transcript	c.532+4530C>T		intron_variant		ENST00000373563.9

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ13	ENST00000233826.4 linkuse as main transcript	c.*2225G>A	3_prime_UTR_variant	3/3	1	NM_002242.4	P1	O60928-1
GIGYF2	ENST00000373563.9 linkuse as main transcript	c.532+4530C>T	intron_variant		1	NM_001103146.3	P4	Q6Y7W6-1
	ENST00000427571.1 linkuse as main transcript	n.271+1713G>A	intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0326

AC:

4806

AN:

147358

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.0755

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.0584

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0235

Gnomad MID

AF:

0.0192

Gnomad NFE

AF:

0.0493

Gnomad OTH

AF:

0.0324

GnomAD3 exomes

AF:

0.0329

AC:

4909

AN:

149074

Hom.:

106

AF XY:

0.0346

AC XY:

2777

AN XY:

80296

show subpopulations

Gnomad AFR exome

AF:

0.00962

Gnomad AMR exome

AF:

0.0197

Gnomad ASJ exome

AF:

0.0602

Gnomad EAS exome

AF:

0.000278

Gnomad SAS exome

AF:

0.0309

Gnomad FIN exome

AF:

0.0197

Gnomad NFE exome

AF:

0.0482

Gnomad OTH exome

AF:

0.0406

GnomAD4 exome

AF:

0.0375

AC:

11939

AN:

318694

Hom.:

292

Cov.:

AF XY:

0.0382

AC XY:

6882

AN XY:

180052

show subpopulations

Gnomad4 AFR exome

AF:

0.00904

Gnomad4 AMR exome

AF:

0.0197

Gnomad4 ASJ exome

AF:

0.0573

Gnomad4 EAS exome

AF:

0.000217

Gnomad4 SAS exome

AF:

0.0311

Gnomad4 FIN exome

AF:

0.0199

Gnomad4 NFE exome

AF:

0.0482

Gnomad4 OTH exome

AF:

0.0377

GnomAD4 genome

AF:

0.0326

AC:

4806

AN:

147474

Hom.:

100

Cov.:

AF XY:

0.0310

AC XY:

2232

AN XY:

71902

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.0272

Gnomad4 ASJ

AF:

0.0584

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0259

Gnomad4 FIN

AF:

0.0235

Gnomad4 NFE

AF:

0.0493

Gnomad4 OTH

AF:

0.0321

Alfa

AF:

0.0430

Hom.:

Bravo

AF:

0.0298

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Leber congenital amaurosis 16

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.6

DANN

Benign

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over