2-232747847-C-T

Variant names:

• chr2-232747847-C-T
• rs3817311
• NM_001103146.3:c.171+103C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001103146.3(GIGYF2):​c.171+103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,093,328 control chromosomes in the GnomAD database, including 72,510 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7986 hom., cov: 32)
  • Exomes 𝑓: 0.36 (64524 hom.)
• Consequence: GIGYF2 NM_001103146.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.27
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-232747847-C-T is Benign according to our data. Variant chr2-232747847-C-T is described in ClinVar as Benign. ClinVar VariationId is 1232643.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.604 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.171+103C>T		intron	N/A	NP_001096616.1	Q6Y7W6-1
	GIGYF2	NM_001103147.2		c.171+103C>T		intron	N/A	NP_001096617.1	Q6Y7W6-3
	GIGYF2	NM_015575.4		c.171+103C>T		intron	N/A	NP_056390.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIGYF2	ENST00000373563.9	TSL:1 MANE Select	c.171+103C>T		intron	N/A	ENSP00000362664.5	Q6Y7W6-1
	GIGYF2	ENST00000409451.7	TSL:1	c.171+103C>T		intron	N/A	ENSP00000387170.3	Q6Y7W6-3
	GIGYF2	ENST00000409547.5	TSL:1	c.171+103C>T		intron	N/A	ENSP00000386537.1	Q6Y7W6-1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48121 AN: 151978 Hom.: 7977 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.309

GnomAD4 exome AF: 0.358 AC: 337270 AN: 941232 Hom.: 64524 AF XY: 0.370 AC XY: 179790 AN XY: 486100

African (AFR) AF: 0.272 AC: 6322 AN: 23268

American (AMR) AF: 0.258 AC: 10209 AN: 39588

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 7402 AN: 22330

East Asian (EAS) AF: 0.289 AC: 10200 AN: 35296

South Asian (SAS) AF: 0.629 AC: 45461 AN: 72316

European-Finnish (FIN) AF: 0.243 AC: 9306 AN: 38366

Middle Eastern (MID) AF: 0.408 AC: 1285 AN: 3152

European-Non Finnish (NFE) AF: 0.349 AC: 231628 AN: 663562

Other (OTH) AF: 0.357 AC: 15457 AN: 43354

GnomAD4 genome AF: 0.317 AC: 48145 AN: 152096 Hom.: 7986 Cov.: 32 AF XY: 0.316 AC XY: 23481 AN XY: 74346

African (AFR) AF: 0.266 AC: 11039 AN: 41470

American (AMR) AF: 0.291 AC: 4450 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1162 AN: 3468

East Asian (EAS) AF: 0.333 AC: 1723 AN: 5176

South Asian (SAS) AF: 0.622 AC: 2995 AN: 4814

European-Finnish (FIN) AF: 0.237 AC: 2514 AN: 10590

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23152 AN: 67966

Other (OTH) AF: 0.317 AC: 671 AN: 2114

Alfa AF: 0.326 Hom.: 10398

Bravo AF: 0.308

Asia WGS AF: 0.493 AC: 1713 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.40
DANN	Benign	0.73
PhyloP100		-1.3
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: rs3817311; hg19: chr2-233612557;