rs3816334

Variant names:

• chr2-232844096-A-G
• rs3816334
• NM_001103146.3:c.2940A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-232844096-A-G
• chr2-232844096-A-C
• chr2-232844096-A-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001103146.3(GIGYF2):​c.2940A>G​(p.Gln980Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,601,720 control chromosomes in the GnomAD database, including 332,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35868 hom., cov: 32)
  • Exomes 𝑓: 0.64 (296172 hom.)
• Consequence: GIGYF2 NM_001103146.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.01
• Publications: 32 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: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.179).
• BP6: Variant 2-232844096-A-G is Benign according to our data. Variant chr2-232844096-A-G is described in ClinVar as Benign. ClinVar VariationId is 518336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 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.2940A>G	p.Gln980Gln	synonymous	Exon 24 of 29	NP_001096616.1	Q6Y7W6-1
	GIGYF2	NM_001103147.2		c.3003A>G	p.Gln1001Gln	synonymous	Exon 26 of 31	NP_001096617.1	Q6Y7W6-3
	GIGYF2	NM_015575.4		c.2940A>G	p.Gln980Gln	synonymous	Exon 26 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.2940A>G	p.Gln980Gln	synonymous	Exon 24 of 29	ENSP00000362664.5	Q6Y7W6-1
	GIGYF2	ENST00000409451.7	TSL:1	c.3003A>G	p.Gln1001Gln	synonymous	Exon 26 of 31	ENSP00000387170.3	Q6Y7W6-3
	GIGYF2	ENST00000409547.5	TSL:1	c.2940A>G	p.Gln980Gln	synonymous	Exon 26 of 31	ENSP00000386537.1	Q6Y7W6-1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103784 AN: 151868 Hom.: 35824 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.689

GnomAD2 exomes AF: 0.650 AC: 157128 AN: 241644 AF XY: 0.632

Gnomad AFR exome AF: 0.736

Gnomad AMR exome AF: 0.748

Gnomad ASJ exome AF: 0.664

Gnomad EAS exome AF: 0.673

Gnomad FIN exome AF: 0.765

Gnomad NFE exome AF: 0.659

Gnomad OTH exome AF: 0.654

GnomAD4 exome AF: 0.636 AC: 921477 AN: 1449734 Hom.: 296172 Cov.: 38 AF XY: 0.628 AC XY: 452438 AN XY: 720936

African (AFR) AF: 0.727 AC: 24154 AN: 33206

American (AMR) AF: 0.744 AC: 32793 AN: 44100

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 17229 AN: 25828

East Asian (EAS) AF: 0.708 AC: 28025 AN: 39578

South Asian (SAS) AF: 0.371 AC: 31702 AN: 85446

European-Finnish (FIN) AF: 0.764 AC: 40458 AN: 52972

Middle Eastern (MID) AF: 0.567 AC: 3256 AN: 5744

European-Non Finnish (NFE) AF: 0.640 AC: 706013 AN: 1102942

Other (OTH) AF: 0.632 AC: 37847 AN: 59918

GnomAD4 genome AF: 0.683 AC: 103878 AN: 151986 Hom.: 35868 Cov.: 32 AF XY: 0.684 AC XY: 50846 AN XY: 74294

African (AFR) AF: 0.734 AC: 30413 AN: 41436

American (AMR) AF: 0.710 AC: 10832 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2307 AN: 3470

East Asian (EAS) AF: 0.667 AC: 3438 AN: 5154

South Asian (SAS) AF: 0.377 AC: 1820 AN: 4826

European-Finnish (FIN) AF: 0.767 AC: 8100 AN: 10560

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44767 AN: 67962

Other (OTH) AF: 0.681 AC: 1436 AN: 2108

Alfa AF: 0.676 Hom.: 58319

Bravo AF: 0.691

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Parkinson disease 11, autosomal dominant, susceptibility to (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.9
DANN	Benign	0.22
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=92/8	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

Other links and lift over

dbSNP: rs3816334; hg19: chr2-233708806; COSMIC: COSV65247246;