2-70777524-ATTCC-A

Position:

• chr2-70777524-ATTCC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001004311.3(FIGLA):​c.644+109_644+112del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,471,222 control chromosomes in the GnomAD database, including 382 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (33 hom., cov: 32)
  • Exomes 𝑓: 0.022 (349 hom.)
• Consequence: FIGLA NM_001004311.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0880

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 -10 ACMG points.

• BP6: Variant 2-70777524-ATTCC-A is Benign according to our data. Variant chr2-70777524-ATTCC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1207553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0165 (2509/152306) while in subpopulation NFE AF= 0.0221 (1503/68028). AF 95% confidence interval is 0.0212. There are 33 homozygotes in gnomad4. There are 1322 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2509 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FIGLA	NM_001004311.3	c.644+109_644+112del		intron_variant		ENST00000332372.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIGLA	ENST00000332372.6	c.644+109_644+112del		intron_variant		1	NM_001004311.3	P1

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2508 AN: 152188 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0219 AC: 28894 AN: 1318916 Hom.: 349 AF XY: 0.0220 AC XY: 14315 AN XY: 650130

Gnomad4 AFR exome AF: 0.00292

Gnomad4 AMR exome AF: 0.0121

Gnomad4 ASJ exome AF: 0.0227

Gnomad4 EAS exome AF: 0.000490

Gnomad4 SAS exome AF: 0.0201

Gnomad4 FIN exome AF: 0.0317

Gnomad4 NFE exome AF: 0.0232

Gnomad4 OTH exome AF: 0.0208

GnomAD4 genome AF: 0.0165 AC: 2509 AN: 152306 Hom.: 33 Cov.: 32 AF XY: 0.0178 AC XY: 1322 AN XY: 74474

Gnomad4 AFR AF: 0.00414

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0154

Gnomad4 FIN AF: 0.0367

Gnomad4 NFE AF: 0.0221

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0168 Hom.: 4

Bravo AF: 0.0139

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 25, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs144711401; hg19: chr2-71004656;