rs6731064

Variant names:

• chr2-232856974-A-C
• rs6731064
• NM_001103146.3:c.*114A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001103147.2(GIGYF2):​c.*114A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 811,930 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (94 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (50 hom.)
• Consequence: GIGYF2 NM_001103147.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37
• Publications: 2 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001103147.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF2	NM_001103146.3	MANE Select	c.*114A>C		3_prime_UTR	Exon 29 of 29	NP_001096616.1
	GIGYF2	NM_001103147.2		c.*114A>C		3_prime_UTR	Exon 31 of 31	NP_001096617.1
	GIGYF2	NM_015575.4		c.*114A>C		3_prime_UTR	Exon 31 of 31	NP_056390.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF2	ENST00000373563.9	TSL:1 MANE Select	c.*114A>C		3_prime_UTR	Exon 29 of 29	ENSP00000362664.5
	GIGYF2	ENST00000409451.7	TSL:1	c.*114A>C		3_prime_UTR	Exon 31 of 31	ENSP00000387170.3
	GIGYF2	ENST00000409547.5	TSL:1	c.*114A>C		3_prime_UTR	Exon 31 of 31	ENSP00000386537.1

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2806 AN: 152176 Hom.: 94 Cov.: 32

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00259 AC: 1710 AN: 659636 Hom.: 50 Cov.: 8 AF XY: 0.00208 AC XY: 741 AN XY: 356636

African (AFR) AF: 0.0632 AC: 1145 AN: 18104

American (AMR) AF: 0.00393 AC: 166 AN: 42262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20968

East Asian (EAS) AF: 0.00 AC: 0 AN: 35798

South Asian (SAS) AF: 0.000186 AC: 13 AN: 69746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50730

Middle Eastern (MID) AF: 0.00595 AC: 18 AN: 3024

European-Non Finnish (NFE) AF: 0.000348 AC: 134 AN: 385116

Other (OTH) AF: 0.00691 AC: 234 AN: 33888

GnomAD4 genome AF: 0.0185 AC: 2819 AN: 152294 Hom.: 94 Cov.: 32 AF XY: 0.0179 AC XY: 1333 AN XY: 74468

African (AFR) AF: 0.0638 AC: 2652 AN: 41542

American (AMR) AF: 0.00712 AC: 109 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68020

Other (OTH) AF: 0.0109 AC: 23 AN: 2116

Alfa AF: 0.0109 Hom.: 14

Bravo AF: 0.0202

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		3.4
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs6731064; hg19: chr2-233721684;