2-232756197-CTTTTTT-C

Variant names:

• chr2-232756197-CTTTTTT-C
• rs759525243
• NM_001103146.3:c.268-11_268-6delTTTTTT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001103146.3(GIGYF2):​c.268-11_268-6delTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00385 in 708,800 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 0)
  • Exomes 𝑓: 0.0039 (4 hom.)
• Consequence: GIGYF2 NM_001103146.3 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• 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 -9 ACMG points.

• BP6: Variant 2-232756197-CTTTTTT-C is Benign according to our data. Variant chr2-232756197-CTTTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 3044764.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00351 (360/102680) while in subpopulation EAS AF= 0.0502 (188/3748). AF 95% confidence interval is 0.0443. There are 5 homozygotes in gnomad4. There are 157 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 360 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3	c.268-11_268-6delTTTTTT		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_268-20delTTTTTT		intron_variant	Intron 5 of 28	1	NM_001103146.3	ENSP00000362664.5

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 360 AN: 102714 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.00165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00389

Gnomad ASJ AF: 0.000358

Gnomad EAS AF: 0.0499

Gnomad SAS AF: 0.00308

Gnomad FIN AF: 0.000544

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.00683

GnomAD4 exome AF: 0.00391 AC: 2368 AN: 606120 Hom.: 4 AF XY: 0.00375 AC XY: 1206 AN XY: 321444

Gnomad4 AFR exome AF: 0.00162

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.000499

Gnomad4 EAS exome AF: 0.0320

Gnomad4 SAS exome AF: 0.00286

Gnomad4 FIN exome AF: 0.000623

Gnomad4 NFE exome AF: 0.00230

Gnomad4 OTH exome AF: 0.00695

GnomAD4 genome AF: 0.00351 AC: 360 AN: 102680 Hom.: 5 Cov.: 0 AF XY: 0.00330 AC XY: 157 AN XY: 47572

Gnomad4 AFR AF: 0.00165

Gnomad4 AMR AF: 0.00389

Gnomad4 ASJ AF: 0.000358

Gnomad4 EAS AF: 0.0502

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.000544

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.00677

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GIGYF2-related disorder Benign:1

Mar 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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;