rs11555646

chr2-232735194-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001103146.3(GIGYF2):c.-4A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,591,010 control chromosomes in the GnomAD database, including 105,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7997 hom., cov: 32)
  • Exomes 𝑓: 0.36 (97822 hom.)
• Consequence: GIGYF2 NM_001103146.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.72

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=-0.23).
• BP6: Variant 2-232735194-A-C is Benign according to our data. Variant chr2-232735194-A-C is described in ClinVar as [Benign]. Clinvar id is 1246966.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-232735194-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIGYF2	NM_001103146.3	c.-4A>C		5_prime_UTR_variant	3/29	ENST00000373563.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIGYF2	ENST00000373563.9	c.-4A>C		5_prime_UTR_variant	3/29	1	NM_001103146.3	P4

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48158 AN: 152008 Hom.: 7988 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.310

GnomAD3 exomes AF: 0.349 AC: 87432 AN: 250634 Hom.: 16996 AF XY: 0.367 AC XY: 49758 AN XY: 135454

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.251

Gnomad ASJ exome AF: 0.337

Gnomad EAS exome AF: 0.326

Gnomad SAS exome AF: 0.638

Gnomad FIN exome AF: 0.238

Gnomad NFE exome AF: 0.339

Gnomad OTH exome AF: 0.344

GnomAD4 exome AF: 0.358 AC: 515414 AN: 1438884 Hom.: 97822 Cov.: 27 AF XY: 0.367 AC XY: 263075 AN XY: 717100

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.628

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.362

GnomAD4 genome AF: 0.317 AC: 48182 AN: 152126 Hom.: 7997 Cov.: 32 AF XY: 0.316 AC XY: 23515 AN XY: 74386

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.318

Alfa AF: 0.332 Hom.: 11371

Bravo AF: 0.309

Asia WGS AF: 0.494 AC: 1716 AN: 3478

EpiCase AF: 0.347

EpiControl AF: 0.344

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 22, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
Cadd	Benign	16
Dann	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs11555646; hg19: chr2-233599904; COSMIC: COSV65247676; COSMIC: COSV65247676;