Variant chr2-232735194-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001103146.3(GIGYF2):c.-4A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,591,010 control chromosomes in the GnomAD database, including 105,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 7997 hom., cov: 32)

Exomes 𝑓: 0.36 ( 97822 hom. )

Consequence

GIGYF2
NM_001103146.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.72

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 2-232735194-A-C is Benign according to our data. Variant chr2-232735194-A-C is described in ClinVar as [Benign]. Clinvar id is 1246966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232735194-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIGYF2	NM_001103146.3 linkuse as main transcript	c.-4A>C		5_prime_UTR_variant	3/29	ENST00000373563.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIGYF2	ENST00000373563.9 linkuse as main transcript	c.-4A>C		5_prime_UTR_variant	3/29	1	NM_001103146.3	P4	Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48158

AN:

152008

Hom.:

7988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.333

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.366

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.310

GnomAD3 exomes

AF:

0.349

AC:

87432

AN:

250634

Hom.:

16996

AF XY:

0.367

AC XY:

49758

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.251

Gnomad ASJ exome

AF:

0.337

Gnomad EAS exome

AF:

0.326

Gnomad SAS exome

AF:

0.638

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.339

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.358

AC:

515414

AN:

1438884

Hom.:

97822

Cov.:

AF XY:

0.367

AC XY:

263075

AN XY:

717100

show subpopulations

Gnomad4 AFR exome

AF:

0.267

Gnomad4 AMR exome

AF:

0.256

Gnomad4 ASJ exome

AF:

0.331

Gnomad4 EAS exome

AF:

0.291

Gnomad4 SAS exome

AF:

0.628

Gnomad4 FIN exome

AF:

0.239

Gnomad4 NFE exome

AF:

0.352

Gnomad4 OTH exome

AF:

0.362

GnomAD4 genome

AF:

0.317

AC:

48182

AN:

152126

Hom.:

7997

Cov.:

AF XY:

0.316

AC XY:

23515

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.266

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.337

Gnomad4 EAS

AF:

0.333

Gnomad4 SAS

AF:

0.623

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.318

Alfa

AF:

0.332

Hom.:

11371

Bravo

AF:

0.309

Asia WGS

AF:

0.494

AC:

1716

AN:

3478

EpiCase

AF:

0.347

EpiControl

AF:

0.344

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 22, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over