rs254285

Positions:

• chr5-132862595-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005260.7(GDF9):​c.398-39G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 1,531,450 control chromosomes in the GnomAD database, including 604,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.89 (60600 hom., cov: 30)
  • Exomes 𝑓: 0.88 (543752 hom.)
• Consequence: GDF9 NM_005260.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.469

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-132862595-C-G is Benign according to our data. Variant chr5-132862595-C-G is described in ClinVar as [Benign]. Clinvar id is 1232056.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF9	NM_005260.7	c.398-39G>C		intron_variant		ENST00000687138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF9	ENST00000687138.1	c.398-39G>C		intron_variant			NM_005260.7	P2

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134830 AN: 151984 Hom.: 60544 Cov.: 30

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.911

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.888

GnomAD3 exomes AF: 0.828 AC: 191959 AN: 231764 Hom.: 81738 AF XY: 0.840 AC XY: 106908 AN XY: 127232

Gnomad AFR exome AF: 0.979

Gnomad AMR exome AF: 0.629

Gnomad ASJ exome AF: 0.913

Gnomad EAS exome AF: 0.543

Gnomad SAS exome AF: 0.888

Gnomad FIN exome AF: 0.754

Gnomad NFE exome AF: 0.900

Gnomad OTH exome AF: 0.863

GnomAD4 exome AF: 0.884 AC: 1219690 AN: 1379350 Hom.: 543752 Cov.: 22 AF XY: 0.886 AC XY: 612272 AN XY: 690864

Gnomad4 AFR exome AF: 0.981

Gnomad4 AMR exome AF: 0.649

Gnomad4 ASJ exome AF: 0.914

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.891

Gnomad4 FIN exome AF: 0.762

Gnomad4 NFE exome AF: 0.906

Gnomad4 OTH exome AF: 0.876

GnomAD4 genome AF: 0.887 AC: 134945 AN: 152100 Hom.: 60600 Cov.: 30 AF XY: 0.878 AC XY: 65219 AN XY: 74310

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.911

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.902

Gnomad4 OTH AF: 0.886

Alfa AF: 0.896 Hom.: 11264

Bravo AF: 0.888

Asia WGS AF: 0.721 AC: 2511 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.30
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs254285; hg19: chr5-132198287; COSMIC: COSV51526807; COSMIC: COSV51526807;