chr2-70785602-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001004311.3(FIGLA):c.422G>C(p.Ser141Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 1,613,180 control chromosomes in the GnomAD database, including 273,140 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 33588 hom., cov: 32)

Exomes 𝑓: 0.57 ( 239552 hom. )

Consequence

FIGLA
NM_001004311.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.52

Publications

26 publications found

Variant links:

Genes affected

FIGLA (HGNC:24669): (folliculogenesis specific bHLH transcription factor) This gene encodes a protein that functions in postnatal oocyte-specific gene expression. The protein is a basic helix-loop-helix transcription factor that regulates multiple oocyte-specific genes, including genes involved in folliculogenesis and those that encode the zona pellucida. Mutations in this gene cause premature ovarian failure type 6. [provided by RefSeq, Sep 2009]

FIGLA Gene-Disease associations (from GenCC):

premature ovarian failure 6
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

FIGLA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.066784E-7).

BP6

Variant 2-70785602-C-G is Benign according to our data. Variant chr2-70785602-C-G is described in ClinVar as [Benign]. Clinvar id is 336909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGLA	NM_001004311.3 link	c.422G>C	p.Ser141Thr	missense_variant	Exon 3 of 5	ENST00000332372.6	NP_001004311.2	Q6QHK4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGLA	ENST00000332372.6 link	c.422G>C	p.Ser141Thr	missense_variant	Exon 3 of 5	1	NM_001004311.3	ENSP00000333097.6		Q6QHK4

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

99033

AN:

151978

Hom.:

33545

Cov.:

show subpopulations

Gnomad AFR

AF:

0.821

Gnomad AMI

AF:

0.619

Gnomad AMR

AF:

0.648

Gnomad ASJ

AF:

0.535

Gnomad EAS

AF:

0.909

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.642

Gnomad MID

AF:

0.580

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.658

GnomAD2 exomes

AF:

0.625

AC:

155849

AN:

249254

AF XY:

0.616

show subpopulations

Gnomad AFR exome

AF:

0.827

Gnomad AMR exome

AF:

0.684

Gnomad ASJ exome

AF:

0.531

Gnomad EAS exome

AF:

0.910

Gnomad FIN exome

AF:

0.631

Gnomad NFE exome

AF:

0.535

Gnomad OTH exome

AF:

0.592

GnomAD4 exome

AF:

0.565

AC:

825835

AN:

1461084

Hom.:

239552

Cov.:

AF XY:

0.566

AC XY:

411306

AN XY:

726838

show subpopulations

African (AFR)

AF:

0.834

AC:

27915

AN:

33476

American (AMR)

AF:

0.678

AC:

30330

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.527

AC:

13764

AN:

26136

East Asian (EAS)

AF:

0.916

AC:

36381

AN:

39700

South Asian (SAS)

AF:

0.648

AC:

55902

AN:

86236

European-Finnish (FIN)

AF:

0.630

AC:

33626

AN:

53400

Middle Eastern (MID)

AF:

0.615

AC:

3545

AN:

5764

European-Non Finnish (NFE)

AF:

0.530

AC:

588794

AN:

1111302

Other (OTH)

AF:

0.590

AC:

35578

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

18769

37539

56308

75078

93847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.652

AC:

99138

AN:

152096

Hom.:

33588

Cov.:

AF XY:

0.659

AC XY:

48983

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.821

AC:

34074

AN:

41508

American (AMR)

AF:

0.649

AC:

9905

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.535

AC:

1854

AN:

3468

East Asian (EAS)

AF:

0.909

AC:

4714

AN:

5184

South Asian (SAS)

AF:

0.673

AC:

3243

AN:

4820

European-Finnish (FIN)

AF:

0.642

AC:

6784

AN:

10566

Middle Eastern (MID)

AF:

0.579

AC:

169

AN:

292

European-Non Finnish (NFE)

AF:

0.536

AC:

36437

AN:

67970

Other (OTH)

AF:

0.661

AC:

1395

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1685

3370

5056

6741

8426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.561

Hom.:

18542

Bravo

AF:

0.664

TwinsUK

AF:

0.529

AC:

1960

ALSPAC

AF:

0.530

AC:

2041

ESP6500AA

AF:

0.814

AC:

3225

ESP6500EA

AF:

0.538

AC:

4492

ExAC

AF:

0.623

AC:

75295

Asia WGS

AF:

0.782

AC:

2720

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Premature ovarian failure 6

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25314148) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

6.9

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.077

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.18

MetaRNN

Benign

7.1e-7

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.2

PhyloP100

1.5

PrimateAI

Benign

0.30

PROVEAN

Benign

0.66

REVEL

Benign

0.19

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.017

MPC

0.081

ClinPred

0.011

GERP RS

3.2

Varity_R

0.047

gMVP

0.20

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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chr2-70785602-C-G

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