chr2-232747873-C-A

Position:

• chr2-232747873-C-A

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.171+129C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 868,698 control chromosomes in the GnomAD database, including 2,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (598 hom., cov: 33)
  • Exomes 𝑓: 0.064 (1795 hom.)
• Consequence: GIGYF2 NM_001103146.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.195

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=-0.75).
• BP6: Variant 2-232747873-C-A is Benign according to our data. Variant chr2-232747873-C-A is described in ClinVar as [Benign]. Clinvar id is 1222110.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIGYF2	NM_001103146.3	c.171+129C>A		intron_variant		ENST00000373563.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIGYF2	ENST00000373563.9	c.171+129C>A		intron_variant		1	NM_001103146.3	P4

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11913 AN: 152088 Hom.: 596 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.0494

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0577

Gnomad OTH AF: 0.0674

GnomAD4 exome AF: 0.0637 AC: 45626 AN: 716490 Hom.: 1795 AF XY: 0.0630 AC XY: 23735 AN XY: 376680

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.0466

Gnomad4 ASJ exome AF: 0.0192

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.0597

Gnomad4 FIN exome AF: 0.0779

Gnomad4 NFE exome AF: 0.0570

Gnomad4 OTH exome AF: 0.0669

GnomAD4 genome AF: 0.0784 AC: 11929 AN: 152208 Hom.: 598 Cov.: 33 AF XY: 0.0798 AC XY: 5942 AN XY: 74420

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0493

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.0695

Gnomad4 FIN AF: 0.0789

Gnomad4 NFE AF: 0.0577

Gnomad4 OTH AF: 0.0672

Alfa AF: 0.0536 Hom.: 170

Bravo AF: 0.0801

Asia WGS AF: 0.0990 AC: 345 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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.37
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3817310; hg19: chr2-233612583;