chr2-70777956-A-G

Position:

• chr2-70777956-A-G

Variant summary

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

The NM_001004311.3(FIGLA):​c.610-285T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 152,202 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.040 (195 hom., cov: 32)
• Consequence: FIGLA NM_001004311.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.106

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 2-70777956-A-G is Benign according to our data. Variant chr2-70777956-A-G is described in ClinVar as [Benign]. Clinvar id is 1249607.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIGLA	NM_001004311.3	c.610-285T>C		intron_variant		ENST00000332372.6	NP_001004311.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIGLA	ENST00000332372.6	c.610-285T>C		intron_variant		1	NM_001004311.3	ENSP00000333097	P1

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6096 AN: 152084 Hom.: 195 Cov.: 32

Gnomad AFR AF: 0.0867

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0227

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0401 AC: 6104 AN: 152202 Hom.: 195 Cov.: 32 AF XY: 0.0404 AC XY: 3002 AN XY: 74396

Gnomad4 AFR AF: 0.0867

Gnomad4 AMR AF: 0.0226

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0158

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.0225

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0305 Hom.: 19

Bravo AF: 0.0406

Asia WGS AF: 0.0140 AC: 50 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

Feb 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.7
DANN	Benign	0.79

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: rs79211746; hg19: chr2-71005088;