NM_002979.5:c.69+7C>A

Variant names:

• chr1-52927472-C-A
• rs1381255788
• NM_002979.5:c.69+7C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_002979.5(SCP2):​c.69+7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SCP2 NM_002979.5 splice_region, intron
• Scores: Splicing: ADA: 0.00004397
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.868
• 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-52927472-C-A is Benign according to our data. Variant chr1-52927472-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1537295.Status of the report is criteria_provided_single_submitter, 1 stars.

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.69+7C>A		splice_region intron	N/A	NP_002970.2
	SCP2	NM_001193599.2		c.69+7C>A		splice_region intron	N/A	NP_001180528.1	P22307-8
	SCP2	NM_001193600.2		c.69+7C>A		splice_region intron	N/A	NP_001180529.1	P22307-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCP2	ENST00000371514.8	TSL:1 MANE Select	c.69+7C>A		splice_region intron	N/A	ENSP00000360569.3	P22307-1
	SCP2	ENST00000371509.8	TSL:1	c.69+7C>A		splice_region intron	N/A	ENSP00000360564.4	P22307-7
	SCP2	ENST00000371513.9	TSL:1	c.69+7C>A		splice_region intron	N/A	ENSP00000360568.5	P22307-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000480 AC: 1 AN: 208330 AF XY: 0.00000894

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000335

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439698 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 713758

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33268

American (AMR) AF: 0.0000243 AC: 1 AN: 41154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25610

East Asian (EAS) AF: 0.00 AC: 0 AN: 38968

South Asian (SAS) AF: 0.00 AC: 0 AN: 82352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101448

Other (OTH) AF: 0.00 AC: 0 AN: 59592

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.8
DANN	Benign	0.90
PhyloP100		-0.87
PromoterAI		0.00050	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000044
dbscSNV1_RF	Benign	0.0040
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: rs1381255788; hg19: chr1-53393144;