22-20431972-A-G

Position:

• chr22-20431972-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_182895.5(SCARF2):​c.190T>C​(p.Cys64Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: SCARF2 NM_182895.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 3.53

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98
• PP5: Variant 22-20431972-A-G is Pathogenic according to our data. Variant chr22-20431972-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 144050.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-20431972-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCARF2	NM_182895.5	c.190T>C	p.Cys64Arg	missense_variant	2/11	ENST00000622235.5
SCARF2	NM_153334.7	c.190T>C	p.Cys64Arg	missense_variant	2/11
SCARF2	XM_047441585.1	c.304T>C	p.Cys102Arg	missense_variant	2/11
SCARF2	XM_017029065.3	c.190T>C	p.Cys64Arg	missense_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCARF2	ENST00000622235.5	c.190T>C	p.Cys64Arg	missense_variant	2/11	1	NM_182895.5	P1
SCARF2	ENST00000623402.1	c.190T>C	p.Cys64Arg	missense_variant	2/11	1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Van den Ende-Gupta syndrome Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	May 01, 2014	- -
Pathogenic, no assertion criteria provided	research	University of Washington Center for Mendelian Genomics, University of Washington	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	.;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.69	T;T
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Pathogenic	5.2	H;H
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.93	D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.84
MutPred		0.90		Gain of MoRF binding (P = 0.0115);Gain of MoRF binding (P = 0.0115);
MVP		0.28
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.81
gMVP		1.0

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: rs587777657; hg19: chr22-20786259;