NM_001103146.3:c.268-14_268-6dupTTTTTTTTT

Variant names:

• chr2-232756197-C-CTTTTTTTTT
• rs759525243
• NM_001103146.3:c.268-14_268-6dupTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001103146.3(GIGYF2):​c.268-14_268-6dupTTTTTTTTT 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 0.00097 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00089 (1 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 100 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3	c.268-14_268-6dupTTTTTTTTT		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_268-25insTTTTTTTTT		intron_variant	Intron 5 of 28	1	NM_001103146.3	ENSP00000362664.5

Frequencies

GnomAD3 genomes AF: 0.000974 AC: 100 AN: 102678 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000500

Gnomad AMI AF: 0.00411

Gnomad AMR AF: 0.000687

Gnomad ASJ AF: 0.00108

Gnomad EAS AF: 0.000797

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000272

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00135

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000892 AC: 542 AN: 607434 Hom.: 1 Cov.: 0 AF XY: 0.000931 AC XY: 300 AN XY: 322074

Gnomad4 AFR exome AF: 0.000741

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.000498

Gnomad4 EAS exome AF: 0.00105

Gnomad4 SAS exome AF: 0.00228

Gnomad4 FIN exome AF: 0.000568

Gnomad4 NFE exome AF: 0.000748

Gnomad4 OTH exome AF: 0.000808

GnomAD4 genome AF: 0.000974 AC: 100 AN: 102644 Hom.: 0 Cov.: 0 AF XY: 0.00109 AC XY: 52 AN XY: 47558

Gnomad4 AFR AF: 0.000499

Gnomad4 AMR AF: 0.000687

Gnomad4 ASJ AF: 0.00108

Gnomad4 EAS AF: 0.000801

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000272

Gnomad4 NFE AF: 0.00135

Gnomad4 OTH AF: 0.00

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;