Genetic Variant NM_001103146.3:c.3855G>A (chr2-232856815-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001103146.3(GIGYF2):c.3855G>A(p.Ser1285Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,613,144 control chromosomes in the GnomAD database, including 332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.016 ( 28 hom., cov: 32)

Exomes 𝑓: 0.018 ( 304 hom. )

Consequence

GIGYF2
NM_001103146.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.840

Publications

4 publications found

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 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

GIGYF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 2-232856815-G-A is Benign according to our data. Variant chr2-232856815-G-A is described in ClinVar as Benign. ClinVar VariationId is 3038024.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.84 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0155 (2365/152182) while in subpopulation NFE AF = 0.0193 (1311/68002). AF 95% confidence interval is 0.0184. There are 28 homozygotes in GnomAd4. There are 1288 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2365 AD,Unknown gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GIGYF2	NM_001103146.3	MANE Select	c.3855G>A	p.Ser1285Ser	synonymous	Exon 29 of 29	NP_001096616.1
GIGYF2	NM_001103147.2		c.3918G>A	p.Ser1306Ser	synonymous	Exon 31 of 31	NP_001096617.1
GIGYF2	NM_015575.4		c.3855G>A	p.Ser1285Ser	synonymous	Exon 31 of 31	NP_056390.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GIGYF2	ENST00000373563.9	TSL:1 MANE Select	c.3855G>A	p.Ser1285Ser	synonymous	Exon 29 of 29	ENSP00000362664.5
GIGYF2	ENST00000409451.7	TSL:1	c.3918G>A	p.Ser1306Ser	synonymous	Exon 31 of 31	ENSP00000387170.3
GIGYF2	ENST00000409547.5	TSL:1	c.3855G>A	p.Ser1285Ser	synonymous	Exon 31 of 31	ENSP00000386537.1

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2367

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0563

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0193

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.0168

AC:

4234

AN:

251366

AF XY:

0.0168

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.00645

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0589

Gnomad NFE exome

AF:

0.0189

Gnomad OTH exome

AF:

0.0189

GnomAD4 exome

AF:

0.0184

AC:

26888

AN:

1460962

Hom.:

304

Cov.:

AF XY:

0.0181

AC XY:

13126

AN XY:

726860

show subpopulations

African (AFR)

AF:

0.00254

AC:

AN:

33466

American (AMR)

AF:

0.0120

AC:

535

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00612

AC:

160

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00519

AC:

448

AN:

86250

European-Finnish (FIN)

AF:

0.0579

AC:

3093

AN:

53414

Middle Eastern (MID)

AF:

0.00503

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0194

AC:

21586

AN:

1111134

Other (OTH)

AF:

0.0158

AC:

952

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

1242

2484

3727

4969

6211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

798

1596

2394

3192

3990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0155

AC:

2365

AN:

152182

Hom.:

Cov.:

AF XY:

0.0173

AC XY:

1288

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.00323

AC:

134

AN:

41520

American (AMR)

AF:

0.0172

AC:

263

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00477

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0563

AC:

596

AN:

10586

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0193

AC:

1311

AN:

68002

Other (OTH)

AF:

0.0109

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

119

238

358

477

596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0171

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GIGYF2-related disorder

Benign:1

Apr 15, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.1

(source)

DANN

Benign

0.87

PhyloP100

-0.84

PromoterAI

-0.0020

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over