NM_001103146.3:c.268-9_268-6dupTTTT

Variant names:

• chr2-232756197-C-CTTTT
• rs759525243
• NM_001103146.3:c.268-9_268-6dupTTTT

Variant summary

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

The NM_001103146.3(GIGYF2):​c.268-9_268-6dupTTTT 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 0.00033 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0020 (2 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 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3	c.268-9_268-6dupTTTT		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_268-25insTTTT		intron_variant	Intron 5 of 28	1	NM_001103146.3	ENSP00000362664.5

Frequencies

GnomAD3 genomes AF: 0.000331 AC: 34 AN: 102712 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000358

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000272

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000418

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00202 AC: 1226 AN: 606668 Hom.: 2 Cov.: 0 AF XY: 0.00215 AC XY: 693 AN XY: 321640

Gnomad4 AFR exome AF: 0.00189

Gnomad4 AMR exome AF: 0.00218

Gnomad4 ASJ exome AF: 0.00231

Gnomad4 EAS exome AF: 0.00130

Gnomad4 SAS exome AF: 0.00583

Gnomad4 FIN exome AF: 0.000812

Gnomad4 NFE exome AF: 0.00171

Gnomad4 OTH exome AF: 0.00202

GnomAD4 genome AF: 0.000331 AC: 34 AN: 102678 Hom.: 0 Cov.: 0 AF XY: 0.000294 AC XY: 14 AN XY: 47566

Gnomad4 AFR AF: 0.000269

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000358

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000272

Gnomad4 NFE AF: 0.000418

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;