rs921055

Positions:

• chr2-232832627-A-C

Variant summary

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

The NM_001103146.3(GIGYF2):​c.2530-230A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,090 control chromosomes in the GnomAD database, including 6,442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (6442 hom., cov: 32)
• Consequence: GIGYF2 NM_001103146.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.560

Genes affected

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-232832627-A-C is Benign according to our data. Variant chr2-232832627-A-C is described in ClinVar as [Benign]. Clinvar id is 1233472.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIGYF2	NM_001103146.3	c.2530-230A>C		intron_variant		ENST00000373563.9	NP_001096616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9	c.2530-230A>C		intron_variant		1	NM_001103146.3	ENSP00000362664	P4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40905 AN: 151972 Hom.: 6439 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.291

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.269 AC: 40913 AN: 152090 Hom.: 6442 Cov.: 32 AF XY: 0.266 AC XY: 19742 AN XY: 74340

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.287

Alfa AF: 0.319 Hom.: 4625

Bravo AF: 0.268

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.71

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: rs921055; hg19: chr2-233697337;