2-130597849-C-CGCGCACCCCTGTGCCCACCT

Position:

• chr2-130597849-C-CGCGCACCCCTGTGCCCACCT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5

The NM_032545.4(CFC1):​c.362+18_362+19insAGGTGGGCACAGGGGTGCGC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFC1 NM_032545.4 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.0490

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 1 ACMG points.

• PP5: Variant 2-130597849-C-CGCGCACCCCTGTGCCCACCT is Pathogenic according to our data. Variant chr2-130597849-C-CGCGCACCCCTGTGCCCACCT is described in ClinVar as [Pathogenic]. Clinvar id is 5190.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFC1	NM_032545.4	c.362+18_362+19insAGGTGGGCACAGGGGTGCGC		intron_variant		ENST00000259216.6	NP_115934.1
CFC1	NM_001270420.2	c.248-247_248-246insAGGTGGGCACAGGGGTGCGC		intron_variant			NP_001257349.1
CFC1	NM_001270421.2	c.247+792_247+793insAGGTGGGCACAGGGGTGCGC		intron_variant			NP_001257350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFC1	ENST00000259216.6	c.362+18_362+19insAGGTGGGCACAGGGGTGCGC		intron_variant		1	NM_032545.4	ENSP00000259216	P1
CFC1	ENST00000615342.4	c.248-247_248-246insAGGTGGGCACAGGGGTGCGC		intron_variant		5		ENSP00000480526
CFC1	ENST00000621673.4	c.247+792_247+793insAGGTGGGCACAGGGGTGCGC		intron_variant		2		ENSP00000480843

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 664 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 324

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Heterotaxy, visceral, 2, autosomal Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs863223280; hg19: chr2-131355422;