rs10491279

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_005260.7(GDF9):c.546G>A(p.Glu182Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,613,476 control chromosomes in the GnomAD database, including 22,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2267 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20587 hom. )

Consequence

GDF9
NM_005260.7 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.696

Publications

29 publications found

Variant links:

Genes affected

GDF9 (HGNC:4224): (growth differentiation factor 9) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates ovarian function. Reduced expression of this gene may be associated with polycystic ovary syndrome and mutations in this gene may be more common in mothers of dizygotic twins. [provided by RefSeq, Jul 2016]

GDF9 Gene-Disease associations (from GenCC):

premature ovarian failure 14
Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

GDF9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 5-132862408-C-T is Benign according to our data. Variant chr5-132862408-C-T is described in ClinVar as Benign. ClinVar VariationId is 137459.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.696 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF9	NM_005260.7 link	c.546G>A	p.Glu182Glu	synonymous_variant	Exon 2 of 2	ENST00000687138.1	NP_005251.1	O60383

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF9	ENST00000687138.1 link	c.546G>A	p.Glu182Glu	synonymous_variant	Exon 2 of 2		NM_005260.7	ENSP00000510441.1		O60383

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25813

AN:

152000

Hom.:

2265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.0574

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.180

GnomAD2 exomes

AF:

0.141

AC:

35566

AN:

251406

AF XY:

0.138

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.0874

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.164

AC:

239916

AN:

1461358

Hom.:

20587

Cov.:

AF XY:

0.162

AC XY:

117837

AN XY:

726994

show subpopulations

African (AFR)

AF:

0.205

AC:

6867

AN:

33464

American (AMR)

AF:

0.0935

AC:

4182

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

4211

AN:

26126

East Asian (EAS)

AF:

0.138

AC:

5474

AN:

39696

South Asian (SAS)

AF:

0.0645

AC:

5567

AN:

86256

European-Finnish (FIN)

AF:

0.151

AC:

8048

AN:

53400

Middle Eastern (MID)

AF:

0.136

AC:

784

AN:

5768

European-Non Finnish (NFE)

AF:

0.175

AC:

194720

AN:

1111554

Other (OTH)

AF:

0.167

AC:

10063

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

11306

22613

33919

45226

56532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6832

13664

20496

27328

34160

<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:

0.170

AC:

25829

AN:

152118

Hom.:

2267

Cov.:

AF XY:

0.166

AC XY:

12327

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.203

AC:

8438

AN:

41482

American (AMR)

AF:

0.132

AC:

2018

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

525

AN:

3470

East Asian (EAS)

AF:

0.145

AC:

749

AN:

5174

South Asian (SAS)

AF:

0.0577

AC:

278

AN:

4820

European-Finnish (FIN)

AF:

0.154

AC:

1625

AN:

10570

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.171

AC:

11658

AN:

67988

Other (OTH)

AF:

0.178

AC:

375

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1089

2177

3266

4354

5443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<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:

0.170

Hom.:

1515

Bravo

AF:

0.171

Asia WGS

AF:

0.0990

AC:

346

AN:

3478

EpiCase

AF:

0.168

EpiControl

AF:

0.168

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 20, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

GDF9-related disorder

Benign:1

Nov 18, 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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.49

(source)

DANN

Benign

0.50

PhyloP100

-0.70

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over