1-52948080-GGT-TCC

Variant names:

• chr1-52948080-GGT-TCC
• NM_002979.5:c.199_199+2delGGTinsTCC
• SCP2 p.Gly67Cys

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_002979.5(SCP2):​c.199_199+2delGGTinsTCC​(p.Gly67Cys) variant causes a splice donor, missense, splice region, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G67S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCP2 NM_002979.5 splice_donor, missense, splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.03
• Publications: 0 publications found

Genes affected

SCP2 (HGNC:10606): (sterol carrier protein 2) This gene encodes two proteins: sterol carrier protein X (SCPx) and sterol carrier protein 2 (SCP2), as a result of transcription initiation from 2 independently regulated promoters. The transcript initiated from the proximal promoter encodes the longer SCPx protein, and the transcript initiated from the distal promoter encodes the shorter SCP2 protein, with the 2 proteins sharing a common C-terminus. Evidence suggests that the SCPx protein is a peroxisome-associated thiolase that is involved in the oxidation of branched chain fatty acids, while the SCP2 protein is thought to be an intracellular lipid transfer protein. This gene is highly expressed in organs involved in lipid metabolism, and may play a role in Zellweger syndrome, in which cells are deficient in peroxisomes and have impaired bile acid synthesis. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms.[provided by RefSeq, Aug 2010]

SCP2 Gene-Disease associations (from GenCC):

• sterol carrier protein 2 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.04379562 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002979.5. 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
	SCP2	NM_002979.5	MANE Select	c.199_199+2delGGTinsTCC	p.Gly67Cys	splice_donor missense splice_region intron	N/A	NP_002970.2
	SCP2	NM_001193617.2		c.-45_-45+2delGGTinsTCC		splice_region	Exon 2 of 15	NP_001180546.1	P22307-4
	SCP2	NM_001193599.2		c.128-2675_128-2673delGGTinsTCC		intron	N/A	NP_001180528.1	P22307-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCP2	ENST00000371514.8	TSL:1 MANE Select	c.199_199+2delGGTinsTCC	p.Gly67Cys	splice_donor missense splice_region intron	N/A	ENSP00000360569.3	P22307-1
	SCP2	ENST00000371509.8	TSL:1	c.199_199+2delGGTinsTCC	p.Gly67Cys	splice_donor missense splice_region intron	N/A	ENSP00000360564.4	P22307-7
	SCP2	ENST00000371513.9	TSL:1	c.199_199+2delGGTinsTCC	p.Gly67Cys	splice_donor missense splice_region intron	N/A	ENSP00000360568.5	P22307-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-53413752;