2-232747873-C-A

Variant names:

• chr2-232747873-C-A
• rs3817310
• NM_001103146.3:c.171+129C>A

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.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
• Publications: 3 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=-0.75).
• 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 rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3	c.171+129C>A		intron_variant	Intron 4 of 28	ENST00000373563.9	NP_001096616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9	c.171+129C>A		intron_variant	Intron 4 of 28	1	NM_001103146.3	ENSP00000362664.5

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

African (AFR) AF: 0.118 AC: 2182 AN: 18560

American (AMR) AF: 0.0466 AC: 1613 AN: 34604

Ashkenazi Jewish (ASJ) AF: 0.0192 AC: 377 AN: 19628

East Asian (EAS) AF: 0.169 AC: 5483 AN: 32414

South Asian (SAS) AF: 0.0597 AC: 3773 AN: 63250

European-Finnish (FIN) AF: 0.0779 AC: 2673 AN: 34332

Middle Eastern (MID) AF: 0.0244 AC: 64 AN: 2622

European-Non Finnish (NFE) AF: 0.0570 AC: 27083 AN: 475528

Other (OTH) AF: 0.0669 AC: 2378 AN: 35552

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

African (AFR) AF: 0.117 AC: 4870 AN: 41534

American (AMR) AF: 0.0493 AC: 755 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3468

East Asian (EAS) AF: 0.175 AC: 906 AN: 5180

South Asian (SAS) AF: 0.0695 AC: 335 AN: 4820

European-Finnish (FIN) AF: 0.0789 AC: 835 AN: 10580

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0577 AC: 3923 AN: 68004

Other (OTH) AF: 0.0672 AC: 142 AN: 2114

Alfa AF: 0.0577 Hom.: 269

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

Jun 20, 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	-0.75
CADD	Benign	0.37
DANN	Benign	0.78
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3817310; hg19: chr2-233612583;