2-113499344-C-T

Variant names:

• chr2-113499344-C-T
• NM_012184.5:c.88C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012184.5(FOXD4L1):​c.88C>T​(p.Leu30Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,370 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: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FOXD4L1 NM_012184.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

Genes affected

FOXD4L1 (HGNC:18521): (forkhead box D4 like 1) This gene is a member of the forkhead/winged-helix (FOX) family of transcription factors with highly conserved FOX DNA-binding domains. Members of the FOX family of transcription factors are regulators of embryogenesis and may play a role in human cancer. This gene lies in a region of chromosome 2 that surrounds the site where two ancestral chromosomes fused to form human chromosome 2. This region is duplicated elsewhere in the human genome, primarily in subtelomeric and pericentromeric locations, thus mutiple copies of this gene have been found. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=0.055 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD4L1	NM_012184.5	c.88C>T	p.Leu30Leu	synonymous_variant	Exon 1 of 1	ENST00000306507.7	NP_036316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXD4L1	ENST00000306507.7	c.88C>T	p.Leu30Leu	synonymous_variant	Exon 1 of 1	6	NM_012184.5	ENSP00000302756.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459370 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 725998

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.2
DANN	Benign	0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-114256921; COSMIC: COSV52075987; COSMIC: COSV52075987;