NM_182895.5:c.2579G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_182895.5(SCARF2):c.2579G>A(p.Arg860Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000588 in 1,428,640 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

SCARF2
NM_182895.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 1.07

Publications

1 publications found

Variant links:

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)

SCARF2 links:

ENSG00000305663 (HGNC:):

ENSG00000305663 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0113839805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARF2	NM_182895.5 link	c.2579G>A	p.Arg860Lys	missense_variant	Exon 11 of 11	ENST00000622235.5	NP_878315.2	Q96GP6-2
SCARF2	NM_153334.7 link	c.2594G>A	p.Arg865Lys	missense_variant	Exon 11 of 11		NP_699165.3	Q96GP6-1
SCARF2	XM_047441585.1 link	c.2693G>A	p.Arg898Lys	missense_variant	Exon 11 of 11		XP_047297541.1
SCARF2	XM_017029065.3 link	c.*808G>A		3_prime_UTR_variant	Exon 11 of 11		XP_016884554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCARF2	ENST00000622235.5 link	c.2579G>A	p.Arg860Lys	missense_variant	Exon 11 of 11	1	NM_182895.5	ENSP00000477564.2	Q96GP6-2
SCARF2	ENST00000623402.1 link	c.2594G>A	p.Arg865Lys	missense_variant	Exon 11 of 11	1		ENSP00000485276.1	Q96GP6-1
ENSG00000305663	ENST00000812275.1 link	n.32+16C>T		intron_variant	Intron 1 of 1
ENSG00000305663	ENST00000812276.1 link	n.35+16C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000628

AC:

AN:

111542

AF XY:

0.0000918

show subpopulations

Gnomad AFR exome

AF:

0.00146

Gnomad AMR exome

AF:

0.00

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:

0.0000337

AC:

AN:

1276408

Hom.:

Cov.:

AF XY:

0.0000367

AC XY:

AN XY:

626466

show subpopulations

African (AFR)

AF:

0.00146

AC:

AN:

26740

American (AMR)

AF:

0.0000390

AC:

AN:

25652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21070

East Asian (EAS)

AF:

0.00

AC:

AN:

30286

South Asian (SAS)

AF:

0.00

AC:

AN:

65376

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4038

European-Non Finnish (NFE)

AF:

9.80e-7

AC:

AN:

1020518

Other (OTH)

AF:

0.0000387

AC:

AN:

51684

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000269

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.000962

AC:

AN:

41560

American (AMR)

AF:

0.0000654

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000385

ESP6500AA

AF:

0.00111

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000718

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

May 29, 2018

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The R865K variant in the SCARF2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R865K variant is not observed in large population cohorts (Lek et al., 2016). The R865K variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. We interpret R865K as a variant of uncertain significance. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Inborn genetic diseases

Uncertain:1

Apr 19, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2591G>A (p.R864K) alteration is located in exon 11 (coding exon 11) of the SCARF2 gene. This alteration results from a G to A substitution at nucleotide position 2591, causing the arginine (R) at amino acid position 864 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.54

T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.98

PhyloP100

1.1

PrimateAI

Pathogenic

0.81

Sift4G

Benign

0.66

T;T

Vest4

0.14

MVP

0.20

ClinPred

0.056

GERP RS

3.2

Varity_R

0.090

gMVP

0.13

Mutation Taster

=97/3

polymorphism

(source)

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

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NM_182895.5:c.2579G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over