chr2-130598710-T-TCGGCG

Variant names:

• chr2-130598710-T-TCGGCG
• NM_032545.4:c.178_179insCGCCG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032545.4(CFC1):​c.178_179insCGCCG​(p.Glu60AlafsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFC1 NM_032545.4 frameshift
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.494

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFC1	NM_032545.4	c.178_179insCGCCG	p.Glu60AlafsTer4	frameshift_variant	Exon 3 of 6	ENST00000259216.6	NP_115934.1
CFC1	NM_001270420.2	c.178_179insCGCCG	p.Glu60AlafsTer4	frameshift_variant	Exon 3 of 5		NP_001257349.1
CFC1	NM_001270421.2	c.178_179insCGCCG	p.Glu60AlafsTer4	frameshift_variant	Exon 3 of 4		NP_001257350.1
CFC1	XM_011511486.4	c.178_179insCGCCG	p.Glu60AlafsTer4	frameshift_variant	Exon 3 of 4		XP_011509788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFC1	ENST00000259216.6	c.178_179insCGCCG	p.Glu60AlafsTer4	frameshift_variant	Exon 3 of 6	1	NM_032545.4	ENSP00000259216.5
CFC1	ENST00000615342.4	c.178_179insCGCCG	p.Glu60AlafsTer4	frameshift_variant	Exon 3 of 5	5		ENSP00000480526.1
CFC1	ENST00000621673.4	c.178_179insCGCCG	p.Glu60AlafsTer4	frameshift_variant	Exon 3 of 4	2		ENSP00000480843.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1461300 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726986

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Heterotaxy, visceral, 2, autosomal Other:1

-

GenomeConnect-Association for Creatine Deficiencies, Association for Creatine Deficiencies

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant classified as Uncertain significance and reported on 02-14-2020 by Macrogen. GenomeConnect-Association for Creatine Deficiencies assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -

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: chr2-131356283;