NM_001103146.3:c.268-8_268-6dupTTT

Variant names:

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

Variant summary

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

The NM_001103146.3(GIGYF2):​c.268-8_268-6dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0041 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0081 (9 hom.)
• Consequence: GIGYF2 NM_001103146.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876

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 sas. gnomad4_exome allele frequency = 0.00806 (4861/603084) while in subpopulation SAS AF= 0.0214 (1015/47466). AF 95% confidence interval is 0.0203. There are 9 homozygotes in gnomad4_exome. There are 2721 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 416 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3	c.268-8_268-6dupTTT		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.268-26_268-25insTTT		intron_variant	Intron 5 of 28	1	NM_001103146.3	ENSP00000362664.5

Frequencies

GnomAD3 genomes AF: 0.00405 AC: 416 AN: 102680 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00219

Gnomad AMI AF: 0.00683

Gnomad AMR AF: 0.00252

Gnomad ASJ AF: 0.00608

Gnomad EAS AF: 0.000797

Gnomad SAS AF: 0.00342

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00571

Gnomad OTH AF: 0.00152

GnomAD4 exome AF: 0.00806 AC: 4861 AN: 603084 Hom.: 9 Cov.: 0 AF XY: 0.00851 AC XY: 2721 AN XY: 319664

Gnomad4 AFR exome AF: 0.00499

Gnomad4 AMR exome AF: 0.00894

Gnomad4 ASJ exome AF: 0.00829

Gnomad4 EAS exome AF: 0.00367

Gnomad4 SAS exome AF: 0.0214

Gnomad4 FIN exome AF: 0.00505

Gnomad4 NFE exome AF: 0.00724

Gnomad4 OTH exome AF: 0.00685

GnomAD4 genome AF: 0.00405 AC: 416 AN: 102646 Hom.: 0 Cov.: 0 AF XY: 0.00385 AC XY: 183 AN XY: 47552

Gnomad4 AFR AF: 0.00219

Gnomad4 AMR AF: 0.00252

Gnomad4 ASJ AF: 0.00608

Gnomad4 EAS AF: 0.000801

Gnomad4 SAS AF: 0.00345

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00571

Gnomad4 OTH AF: 0.00150

ClinVar

Not reported in ClinVar

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;