2-232734934-C-T

Variant names:

• chr2-232734934-C-T
• rs75911181
• NM_001103146.3:c.-43-221C>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.-43-221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 152,088 control chromosomes in the GnomAD database, including 816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.089 (816 hom., cov: 31)
• Consequence: GIGYF2 NM_001103146.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.185
• Publications: 1 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 2-232734934-C-T is Benign according to our data. Variant chr2-232734934-C-T is described in ClinVar as [Benign]. Clinvar id is 1257999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3	c.-43-221C>T		intron_variant	Intron 2 of 28	ENST00000373563.9	NP_001096616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9	c.-43-221C>T		intron_variant	Intron 2 of 28	1	NM_001103146.3	ENSP00000362664.5

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13468 AN: 151970 Hom.: 807 Cov.: 31

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.0459

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.0901

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0805

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

GnomAD4 genome AF: 0.0887 AC: 13484 AN: 152088 Hom.: 816 Cov.: 31 AF XY: 0.0929 AC XY: 6910 AN XY: 74344

African (AFR) AF: 0.0393 AC: 1630 AN: 41474

American (AMR) AF: 0.0928 AC: 1418 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0459 AC: 159 AN: 3466

East Asian (EAS) AF: 0.124 AC: 640 AN: 5166

South Asian (SAS) AF: 0.278 AC: 1337 AN: 4816

European-Finnish (FIN) AF: 0.0901 AC: 955 AN: 10598

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7106 AN: 67974

Other (OTH) AF: 0.0896 AC: 189 AN: 2110

Alfa AF: 0.0855 Hom.: 75

Bravo AF: 0.0819

Asia WGS AF: 0.234 AC: 812 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 21, 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	3.5
DANN	Benign	0.39
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs75911181; hg19: chr2-233599644;