2-232756197-CTTTTTTTTTTTTTT-CTTT

Variant names:

• chr2-232756197-CTTTTTTTTTTT-C
• rs759525243
• NM_001103146.3:c.268-16_268-6delTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001103146.3(GIGYF2):​c.268-16_268-6delTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 710,634 control chromosomes in the GnomAD database, including 3 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00016 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (2 hom.)
• Consequence: GIGYF2 NM_001103146.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 16 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3	c.268-16_268-6delTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 5 of 28	ENST00000373563.9	NP_001096616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9	c.268-25_268-15delTTTTTTTTTTT		intron_variant	Intron 5 of 28	1	NM_001103146.3	ENSP00000362664.5

Frequencies

GnomAD3 genomes AF: 0.000127 AC: 13 AN: 102710 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000132 AC: 80 AN: 607958 Hom.: 2 AF XY: 0.000124 AC XY: 40 AN XY: 322392

African (AFR) AF: 0.000202 AC: 3 AN: 14868

American (AMR) AF: 0.0000776 AC: 2 AN: 25780

Ashkenazi Jewish (ASJ) AF: 0.000249 AC: 4 AN: 16078

East Asian (EAS) AF: 0.0000318 AC: 1 AN: 31438

South Asian (SAS) AF: 0.0000207 AC: 1 AN: 48302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2268

European-Non Finnish (NFE) AF: 0.000159 AC: 64 AN: 402472

Other (OTH) AF: 0.000168 AC: 5 AN: 29738

GnomAD4 genome AF: 0.000156 AC: 16 AN: 102676 Hom.: 1 Cov.: 0 AF XY: 0.000126 AC XY: 6 AN XY: 47570

African (AFR) AF: 0.000192 AC: 5 AN: 26038

American (AMR) AF: 0.00 AC: 0 AN: 8742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2792

East Asian (EAS) AF: 0.00 AC: 0 AN: 3746

South Asian (SAS) AF: 0.00 AC: 0 AN: 2896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 152

European-Non Finnish (NFE) AF: 0.000152 AC: 8 AN: 52572

Other (OTH) AF: 0.00226 AC: 3 AN: 1330

Alfa AF: 0.00 Hom.: 144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs759525243; hg19: chr2-233620907;