chr2-232747282-A-G

Position:

• chr2-232747282-A-G

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.42-333A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,126 control chromosomes in the GnomAD database, including 2,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2598 hom., cov: 32)
• Consequence: GIGYF2 NM_001103146.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49

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=-0.88).
• BP6: Variant 2-232747282-A-G is Benign according to our data. Variant chr2-232747282-A-G is described in ClinVar as [Benign]. Clinvar id is 1183659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIGYF2	NM_001103146.3	c.42-333A>G		intron_variant		ENST00000373563.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIGYF2	ENST00000373563.9	c.42-333A>G		intron_variant		1	NM_001103146.3	P4

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24703 AN: 152008 Hom.: 2601 Cov.: 32

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.162 AC: 24693 AN: 152126 Hom.: 2598 Cov.: 32 AF XY: 0.163 AC XY: 12140 AN XY: 74352

Gnomad4 AFR AF: 0.0424

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0925

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.194

Alfa AF: 0.205 Hom.: 472

Bravo AF: 0.152

Asia WGS AF: 0.106 AC: 373 AN: 3476

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	-0.88
CADD	Benign	5.3
DANN	Benign	0.47

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: rs35785837; hg19: chr2-233611992;