rs775324034

Variant names:

• chr2-232847517-A-AG
• rs775324034
• NM_001103146.3:c.3630_3631insG

Your query was ambiguous. Multiple possible variants found:

• chr2-232847517-A-AG
• chr2-232847517-A-AGCAG
• chr2-232847517-A-AGCAGCAG
• chr2-232847517-A-AGCAGCAGCAGCAGCAGCAGCTGCCGCAG
• chr2-232847517-A-AGCAGCAGCAGCAGCAGCTGCCGCAG
• chr2-232847517-A-AGCAGCAGCAGCAGCTGCCGCAG
• chr2-232847517-A-AGCAGCAGCTGCCGCAG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 8P and 16B. PVS1 BP6_Very_Strong BA1

The NM_001103146.3(GIGYF2):​c.3630_3631insG​(p.Gln1211AlafsTer46) variant causes a frameshift change. Variant has been reported in ClinVar as Likely benign (★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.17 (237 hom., cov: 0)
  • Exomes 𝑓: 0.12 (1775 hom.)
• Consequence: GIGYF2 NM_001103146.3 frameshift
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.44
• Publications: 3 publications found

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]

GIGYF2 Gene-Disease associations (from GenCC):

• Parkinson disease 11, autosomal dominant, susceptibility to

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• BP6: Variant 2-232847517-A-AG is Benign according to our data. Variant chr2-232847517-A-AG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 402900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001103146.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF2	NM_001103146.3	MANE Select	c.3630_3631insG	p.Gln1211AlafsTer46	frameshift	Exon 27 of 29	NP_001096616.1	Q6Y7W6-1
	GIGYF2	NM_001103147.2		c.3693_3694insG	p.Gln1232AlafsTer46	frameshift	Exon 29 of 31	NP_001096617.1	Q6Y7W6-3
	GIGYF2	NM_015575.4		c.3630_3631insG	p.Gln1211AlafsTer46	frameshift	Exon 29 of 31	NP_056390.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF2	ENST00000373563.9	TSL:1 MANE Select	c.3630_3631insG	p.Gln1211AlafsTer46	frameshift	Exon 27 of 29	ENSP00000362664.5	Q6Y7W6-1
	GIGYF2	ENST00000409451.7	TSL:1	c.3693_3694insG	p.Gln1232AlafsTer46	frameshift	Exon 29 of 31	ENSP00000387170.3	Q6Y7W6-3
	GIGYF2	ENST00000409547.5	TSL:1	c.3630_3631insG	p.Gln1211AlafsTer46	frameshift	Exon 29 of 31	ENSP00000386537.1	Q6Y7W6-1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 5019 AN: 28964 Hom.: 237 Cov.: 0

Gnomad AFR AF: 0.0445

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.185

GnomAD2 exomes AF: 0.0339 AC: 7827 AN: 230696 AF XY: 0.0342

Gnomad AFR exome AF: 0.00395

Gnomad AMR exome AF: 0.0487

Gnomad ASJ exome AF: 0.0136

Gnomad EAS exome AF: 0.129

Gnomad FIN exome AF: 0.0452

Gnomad NFE exome AF: 0.0137

Gnomad OTH exome AF: 0.0250

GnomAD4 exome AF: 0.120 AC: 46437 AN: 386888 Hom.: 1775 Cov.: 0 AF XY: 0.122 AC XY: 23962 AN XY: 196702

African (AFR) AF: 0.0313 AC: 227 AN: 7242

American (AMR) AF: 0.333 AC: 3088 AN: 9282

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 468 AN: 4454

East Asian (EAS) AF: 0.458 AC: 9565 AN: 20892

South Asian (SAS) AF: 0.137 AC: 6720 AN: 48930

European-Finnish (FIN) AF: 0.352 AC: 3620 AN: 10296

Middle Eastern (MID) AF: 0.138 AC: 212 AN: 1536

European-Non Finnish (NFE) AF: 0.0763 AC: 20474 AN: 268468

Other (OTH) AF: 0.131 AC: 2063 AN: 15788

GnomAD4 genome AF: 0.173 AC: 5019 AN: 28976 Hom.: 237 Cov.: 0 AF XY: 0.188 AC XY: 2792 AN XY: 14836

African (AFR) AF: 0.0448 AC: 289 AN: 6456

American (AMR) AF: 0.259 AC: 751 AN: 2898

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 54 AN: 474

East Asian (EAS) AF: 0.439 AC: 1183 AN: 2696

South Asian (SAS) AF: 0.154 AC: 416 AN: 2706

European-Finnish (FIN) AF: 0.367 AC: 813 AN: 2218

Middle Eastern (MID) AF: 0.182 AC: 16 AN: 88

European-Non Finnish (NFE) AF: 0.127 AC: 1385 AN: 10866

Other (OTH) AF: 0.170 AC: 61 AN: 358

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.4
Mutation Taster		=200/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs775324034;

hg19: chr2-233712227;

COSMIC: COSV101004226;

COSMIC: COSV101004226;