chr2-232747847-C-T

Position:

• chr2-232747847-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001103146.3(GIGYF2):​c.171+103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,093,328 control chromosomes in the GnomAD database, including 72,510 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7986 hom., cov: 32)
  • Exomes 𝑓: 0.36 (64524 hom.)
• Consequence: GIGYF2 NM_001103146.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.27

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-232747847-C-T is Benign according to our data. Variant chr2-232747847-C-T is described in ClinVar as [Benign]. Clinvar id is 1232643.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIGYF2	NM_001103146.3	c.171+103C>T		intron_variant		ENST00000373563.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIGYF2	ENST00000373563.9	c.171+103C>T		intron_variant		1	NM_001103146.3	P4

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48121 AN: 151978 Hom.: 7977 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.309

GnomAD4 exome AF: 0.358 AC: 337270 AN: 941232 Hom.: 64524 AF XY: 0.370 AC XY: 179790 AN XY: 486100

Gnomad4 AFR exome AF: 0.272

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.289

Gnomad4 SAS exome AF: 0.629

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.357

GnomAD4 genome AF: 0.317 AC: 48145 AN: 152096 Hom.: 7986 Cov.: 32 AF XY: 0.316 AC XY: 23481 AN XY: 74346

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.317

Alfa AF: 0.330 Hom.: 8166

Bravo AF: 0.308

Asia WGS AF: 0.493 AC: 1713 AN: 3476

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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.40
DANN	Benign	0.73
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: rs3817311; hg19: chr2-233612557;