2-232747331-G-T

Variant names:

• chr2-232747331-G-T
• rs76556984
• NM_001103146.3:c.42-284G>T

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.42-284G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 152,054 control chromosomes in the GnomAD database, including 290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.060 (290 hom., cov: 32)
• Consequence: GIGYF2 NM_001103146.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.329
• Publications: 0 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=-0.86).
• BP6: Variant 2-232747331-G-T is Benign according to our data. Variant chr2-232747331-G-T is described in ClinVar as [Benign]. Clinvar id is 1289767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3	c.42-284G>T		intron_variant	Intron 3 of 28	ENST00000373563.9	NP_001096616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9	c.42-284G>T		intron_variant	Intron 3 of 28	1	NM_001103146.3	ENSP00000362664.5

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9122 AN: 151936 Hom.: 291 Cov.: 32

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.0690

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0479

Gnomad FIN AF: 0.0433

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0591

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

GnomAD4 genome AF: 0.0600 AC: 9116 AN: 152054 Hom.: 290 Cov.: 32 AF XY: 0.0577 AC XY: 4286 AN XY: 74322

African (AFR) AF: 0.0510 AC: 2115 AN: 41470

American (AMR) AF: 0.0476 AC: 727 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0690 AC: 239 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0475 AC: 229 AN: 4816

European-Finnish (FIN) AF: 0.0433 AC: 458 AN: 10566

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0756 AC: 5140 AN: 67976

Other (OTH) AF: 0.0585 AC: 123 AN: 2104

Alfa AF: 0.0701 Hom.: 66

Bravo AF: 0.0589

Asia WGS AF: 0.0270 AC: 94 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	-0.86
CADD	Benign	6.1
DANN	Benign	0.75
PhyloP100		0.33
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: rs76556984; hg19: chr2-233612041;