rs6731064

Positions:

• chr2-232856974-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001103146.3(GIGYF2):​c.*114A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 811,930 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (94 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (50 hom.)
• Consequence: GIGYF2 NM_001103146.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIGYF2	NM_001103146.3	c.*114A>C		3_prime_UTR_variant	29/29	ENST00000373563.9	NP_001096616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9	c.*114A>C		3_prime_UTR_variant	29/29	1	NM_001103146.3	ENSP00000362664	P4

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2806 AN: 152176 Hom.: 94 Cov.: 32

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00259 AC: 1710 AN: 659636 Hom.: 50 Cov.: 8 AF XY: 0.00208 AC XY: 741 AN XY: 356636

Gnomad4 AFR exome AF: 0.0632

Gnomad4 AMR exome AF: 0.00393

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000348

Gnomad4 OTH exome AF: 0.00691

GnomAD4 genome AF: 0.0185 AC: 2819 AN: 152294 Hom.: 94 Cov.: 32 AF XY: 0.0179 AC XY: 1333 AN XY: 74468

Gnomad4 AFR AF: 0.0638

Gnomad4 AMR AF: 0.00712

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0139 Hom.: 9

Bravo AF: 0.0202

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6731064; hg19: chr2-233721684;