chr2-130592943-C-T

Variant names:

• chr2-130592943-C-T
• rs587780887
• NM_032545.4:c.606G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001270420.2(CFC1):​c.491G>A​(p.Trp164*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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: 7)
• Consequence: CFC1 NM_001270420.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 1 publications found

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]

CFC1 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 2, autosomal

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ENSG00000296239 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270420.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFC1	NM_032545.4	MANE Select	c.606G>A	p.Leu202Leu	synonymous	Exon 6 of 6	NP_115934.1	P0CG37
	CFC1	NM_001270420.2		c.491G>A	p.Trp164*	stop_gained	Exon 5 of 5	NP_001257349.1	A0A087WWV2
	CFC1	NM_001270421.2		c.381G>A	p.Leu127Leu	synonymous	Exon 4 of 4	NP_001257350.1	A0A087WX98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFC1	ENST00000259216.6	TSL:1 MANE Select	c.606G>A	p.Leu202Leu	synonymous	Exon 6 of 6	ENSP00000259216.5	P0CG37
	CFC1	ENST00000615342.4	TSL:5	c.491G>A	p.Trp164*	stop_gained	Exon 5 of 5	ENSP00000480526.1	A0A087WWV2
	CFC1	ENST00000621673.4	TSL:2	c.381G>A	p.Leu127Leu	synonymous	Exon 4 of 4	ENSP00000480843.1	A0A087WX98

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 7

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.6
DANN	Benign	0.78
FATHMM_MKL	Benign	0.00084	N
PhyloP100		-2.0
Vest4		0.26
GERP RS		-3.3
Mutation Taster		=100/0	polymorphism

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: rs587780887; hg19: chr2-131350516;