2-130592893-AGTCCCGG-A

Variant names:

• chr2-130592893-AGTCCCGG-A
• NM_032545.4:c.649_655delCCGGGAC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_032545.4(CFC1):​c.649_655delCCGGGAC​(p.Pro217LeufsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 6)
  • Exomes 𝑓: 0.0000071 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFC1 NM_032545.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.431

Genes affected

CFC1 (HGNC:18292): (cryptic, EGF-CFC family member 1) This gene encodes a member of the epidermal growth factor (EGF)- Cripto, Frl-1, and Cryptic (CFC) family, which are involved in signalling during embryonic development. Proteins in this family share a variant EGF-like motif, a conserved cysteine-rich domain, and a C-terminal hydrophobic region. The protein encoded by this gene is necessary for patterning the left-right embryonic axis. Mutations in this gene are associated with defects in organ development, including autosomal visceral heterotaxy and congenital heart disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFC1	NM_032545.4	c.649_655delCCGGGAC	p.Pro217LeufsTer12	frameshift_variant	Exon 6 of 6	ENST00000259216.6	NP_115934.1
CFC1	NM_001270420.2	c.534_540delCCGGGAC	p.Arg179TrpfsTer16	frameshift_variant	Exon 5 of 5		NP_001257349.1
CFC1	NM_001270421.2	c.424_430delCCGGGAC	p.Pro142LeufsTer12	frameshift_variant	Exon 4 of 4		NP_001257350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFC1	ENST00000259216.6	c.649_655delCCGGGAC	p.Pro217LeufsTer12	frameshift_variant	Exon 6 of 6	1	NM_032545.4	ENSP00000259216.5
CFC1	ENST00000615342.4	c.534_540delCCGGGAC	p.Arg179TrpfsTer16	frameshift_variant	Exon 5 of 5	5		ENSP00000480526.1
CFC1	ENST00000621673.4	c.424_430delCCGGGAC	p.Pro142LeufsTer12	frameshift_variant	Exon 4 of 4	2		ENSP00000480843.1

Frequencies

GnomAD3 genomes Cov.: 6

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000715 AC: 3 AN: 419862 Hom.: 0 AF XY: 0.00000455 AC XY: 1 AN XY: 219866

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000179

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Oct 01, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; Frameshift variant predicted to result in abnormal protein length as the last 7 amino acids are replaced with 11 different amino acids -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr2-131350466;