rs786205883

Variant names:

• chr22-20431414-TCGCAGCGCGCGCCCCAG-T
• rs786205883
• NM_182895.5:c.441_457delCTGGGGCGCGCGCTGCG

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_182895.5(SCARF2):​c.441_457delCTGGGGCGCGCGCTGCG​(p.Trp148AlafsTer20) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCARF2 NM_182895.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.54

Genes affected

SCARF2 (HGNC:19869): (scavenger receptor class F member 2) The protein encoded by this gene is similar to SCARF1/SREC-I, a scavenger receptor protein that mediates the binding and degradation of acetylated low density lipoprotein (Ac-LDL). This protein has only little activity of internalizing modified low density lipoproteins (LDL), but it can interact with SCARF1 through its extracellular domain. The association of this protein with SCARF1 is suppressed by the presence of scavenger ligands. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ENSG00000277971 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 22-20431414-TCGCAGCGCGCGCCCCAG-T is Pathogenic according to our data. Variant chr22-20431414-TCGCAGCGCGCGCCCCAG-T is described in ClinVar as [Pathogenic]. Clinvar id is 190239.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARF2	NM_182895.5	c.441_457delCTGGGGCGCGCGCTGCG	p.Trp148AlafsTer20	frameshift_variant	Exon 4 of 11	ENST00000622235.5	NP_878315.2
SCARF2	NM_153334.7	c.441_457delCTGGGGCGCGCGCTGCG	p.Trp148AlafsTer20	frameshift_variant	Exon 4 of 11		NP_699165.3
SCARF2	XM_047441585.1	c.555_571delCTGGGGCGCGCGCTGCG	p.Trp186AlafsTer20	frameshift_variant	Exon 4 of 11		XP_047297541.1
SCARF2	XM_017029065.3	c.441_457delCTGGGGCGCGCGCTGCG	p.Trp148AlafsTer20	frameshift_variant	Exon 4 of 11		XP_016884554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARF2	ENST00000622235.5	c.441_457delCTGGGGCGCGCGCTGCG	p.Trp148AlafsTer20	frameshift_variant	Exon 4 of 11	1	NM_182895.5	ENSP00000477564.2
SCARF2	ENST00000623402.1	c.441_457delCTGGGGCGCGCGCTGCG	p.Trp148AlafsTer20	frameshift_variant	Exon 4 of 11	1		ENSP00000485276.1
ENSG00000277971	ENST00000429594.1	n.178-874_178-858delCTGGGGCGCGCGCTGCG		intron_variant	Intron 1 of 4	5		ENSP00000392268.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Van den Ende-Gupta syndrome Pathogenic:1

May 01, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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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: rs786205883; hg19: chr22-20785701;