rs587777658

chr22-20425444-CT-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The NM_182895.5(SCARF2):c.2531del(p.Gln844ArgfsTer95) 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCARF2 NM_182895.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.03

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0269 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 22-20425444-CT-C is Pathogenic according to our data. Variant chr22-20425444-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 144051.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-20425444-CT-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCARF2	NM_182895.5	c.2531del	p.Gln844ArgfsTer95	frameshift_variant	11/11	ENST00000622235.5
SCARF2	NM_153334.7	c.2546del	p.Gln849ArgfsTer95	frameshift_variant	11/11
SCARF2	XM_047441585.1	c.2645del	p.Gln882ArgfsTer95	frameshift_variant	11/11
SCARF2	XM_017029065.3	c.*760del		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARF2	ENST00000622235.5	c.2531del	p.Gln844ArgfsTer95	frameshift_variant	11/11	1	NM_182895.5	P1
SCARF2	ENST00000623402.1	c.2546del	p.Gln849ArgfsTer95	frameshift_variant	11/11	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2014

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs587777658; hg19: chr22-20779734;