chr2-232832627-A-C

Variant names:

• chr2-232832627-A-C
• rs921055
• NM_001103146.3:c.2530-230A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

GIGYF2 Gene-Disease associations (from GenCC):

• Parkinson disease 11, autosomal dominant, susceptibility to

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3	c.2530-230A>C		intron_variant	Intron 21 of 28	ENST00000373563.9	NP_001096616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9	c.2530-230A>C		intron_variant	Intron 21 of 28	1	NM_001103146.3	ENSP00000362664.5

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

African (AFR) AF: 0.114 AC: 4742 AN: 41522

American (AMR) AF: 0.339 AC: 5184 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1179 AN: 3472

East Asian (EAS) AF: 0.119 AC: 615 AN: 5176

South Asian (SAS) AF: 0.125 AC: 606 AN: 4830

European-Finnish (FIN) AF: 0.316 AC: 3338 AN: 10552

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24252 AN: 67940

Other (OTH) AF: 0.287 AC: 606 AN: 2110

Alfa AF: 0.321 Hom.: 5137

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

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.71
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs921055; hg19: chr2-233697337;