2-232756197-CTTTTTTTTTTTT-CTTTTTTTTT

Variant names:

• chr2-232756197-CTTT-C
• rs759525243
• NM_001103146.3:c.268-8_268-6delTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001103146.3(GIGYF2):​c.268-8_268-6delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00878 in 696,916 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000029 (0 hom., cov: 0)
  • Exomes 𝑓: 0.010 (0 hom.)
• Consequence: GIGYF2 NM_001103146.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0103 (6113/594248) while in subpopulation AFR AF= 0.0184 (266/14462). AF 95% confidence interval is 0.0166. There are 0 homozygotes in gnomad4_exome. There are 3105 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 6113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3	c.268-8_268-6delTTT		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_268-23delTTT		intron_variant	Intron 5 of 28	1	NM_001103146.3	ENSP00000362664.5

Frequencies

GnomAD3 genomes AF: 0.0000292 AC: 3 AN: 102702 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000115

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0103 AC: 6113 AN: 594248 Hom.: 0 AF XY: 0.00985 AC XY: 3105 AN XY: 315254

Gnomad4 AFR exome AF: 0.0184

Gnomad4 AMR exome AF: 0.0104

Gnomad4 ASJ exome AF: 0.00990

Gnomad4 EAS exome AF: 0.0143

Gnomad4 SAS exome AF: 0.00787

Gnomad4 FIN exome AF: 0.00876

Gnomad4 NFE exome AF: 0.0100

Gnomad4 OTH exome AF: 0.0118

GnomAD4 genome AF: 0.0000292 AC: 3 AN: 102668 Hom.: 0 Cov.: 0 AF XY: 0.0000420 AC XY: 2 AN XY: 47566

Gnomad4 AFR AF: 0.000115

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs759525243; hg19: chr2-233620907;