chr22-20431972-A-G

Variant names:

• chr22-20431972-A-G
• rs587777657
• NM_182895.5:c.190T>C

Variant summary

Our verdict is Likely pathogenic. The variant received 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
• Publications: 3 publications found

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]

SCARF2 Gene-Disease associations (from GenCC):

• van den Ende-Gupta syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000277971 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 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 VariationId is 144050.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182895.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARF2	NM_182895.5	MANE Select	c.190T>C	p.Cys64Arg	missense	Exon 2 of 11	NP_878315.2
	SCARF2	NM_153334.7		c.190T>C	p.Cys64Arg	missense	Exon 2 of 11	NP_699165.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARF2	ENST00000622235.5	TSL:1 MANE Select	c.190T>C	p.Cys64Arg	missense	Exon 2 of 11	ENSP00000477564.2
	SCARF2	ENST00000623402.1	TSL:1	c.190T>C	p.Cys64Arg	missense	Exon 2 of 11	ENSP00000485276.1
	ENSG00000277971	ENST00000429594.1	TSL:5	n.178-1415T>C		intron	N/A	ENSP00000392268.1

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

May 01, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

University of Washington Center for Mendelian Genomics, University of Washington

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Pathogenic	5.2	H
PhyloP100		3.5
PrimateAI	Pathogenic	0.93	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.90		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
Mutation Taster		=2/98	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs587777657; hg19: chr22-20786259;