Genetic Variant NM_001103146.3:c.268-6dupT (chr2-232756197-C-CT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001103146.3(GIGYF2):c.268-6dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 7850 hom., cov: 0)

Exomes 𝑓: 0.20 ( 356 hom. )

Consequence

GIGYF2
NM_001103146.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.876

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 link	c.268-6dupT		splice_region_variant, intron_variant	Intron 5 of 28	ENST00000373563.9	NP_001096616.1	Q6Y7W6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9 link	c.268-26_268-25insT		intron_variant	Intron 5 of 28	1	NM_001103146.3	ENSP00000362664.5		Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

38026

AN:

102874

Hom.:

7851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.386

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.486

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.440

Gnomad OTH

AF:

0.359

GnomAD4 exome

AF:

0.196

AC:

116562

AN:

594856

Hom.:

356

Cov.:

AF XY:

0.197

AC XY:

62135

AN XY:

315158

show subpopulations

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.213

Gnomad4 OTH exome

AF:

0.208

GnomAD4 genome

AF:

0.370

AC:

38001

AN:

102840

Hom.:

7850

Cov.:

AF XY:

0.353

AC XY:

16823

AN XY:

47660

show subpopulations

Gnomad4 AFR

AF:

0.284

Gnomad4 AMR

AF:

0.305

Gnomad4 ASJ

AF:

0.442

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.487

Gnomad4 FIN

AF:

0.142

Gnomad4 NFE

AF:

0.440

Gnomad4 OTH

AF:

0.357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over