2-70777362-A-G

Variant names:

• chr2-70777362-A-G
• rs56135050
• NM_001004311.3:c.*5T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004311.3(FIGLA):​c.*5T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000752 in 1,329,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: FIGLA NM_001004311.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.970
• Publications: 7 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGLA	NM_001004311.3	c.*5T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000332372.6	NP_001004311.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGLA	ENST00000332372.6	c.*5T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_001004311.3	ENSP00000333097.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.52e-7 AC: 1 AN: 1329812 Hom.: 0 Cov.: 25 AF XY: 0.00000152 AC XY: 1 AN XY: 657230

African (AFR) AF: 0.00 AC: 0 AN: 29716

American (AMR) AF: 0.00 AC: 0 AN: 25930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23808

East Asian (EAS) AF: 0.00 AC: 0 AN: 35254

South Asian (SAS) AF: 0.00 AC: 0 AN: 67802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5410

European-Non Finnish (NFE) AF: 9.63e-7 AC: 1 AN: 1038114

Other (OTH) AF: 0.00 AC: 0 AN: 55096

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		0.97

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

Other links and lift over

dbSNP: rs56135050; hg19: chr2-71004494;