Genetic Variant SCARF2:p.Arg860Thr (chr22-20425397-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182895.5(SCARF2):c.2579G>C(p.Arg860Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000783 in 1,276,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R860K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

SCARF2
NM_182895.5 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15125886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARF2	NM_182895.5 link	c.2579G>C	p.Arg860Thr	missense_variant	Exon 11 of 11	ENST00000622235.5	NP_878315.2	Q96GP6-2
SCARF2	NM_153334.7 link	c.2594G>C	p.Arg865Thr	missense_variant	Exon 11 of 11		NP_699165.3	Q96GP6-1
SCARF2	XM_047441585.1 link	c.2693G>C	p.Arg898Thr	missense_variant	Exon 11 of 11		XP_047297541.1
SCARF2	XM_017029065.3 link	c.*808G>C		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>C	p.Arg860Thr	missense_variant	Exon 11 of 11	1	NM_182895.5	ENSP00000477564.2	Q96GP6-2
SCARF2	ENST00000623402.1 link	c.2594G>C	p.Arg865Thr	missense_variant	Exon 11 of 11	1		ENSP00000485276.1	Q96GP6-1
ENSG00000305663	ENST00000812275.1 link	n.32+16C>G		intron_variant	Intron 1 of 1
ENSG00000305663	ENST00000812276.1 link	n.35+16C>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.83e-7

AC:

AN:

1276408

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

626466

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

26740

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

51684

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.94

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.66

T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

PhyloP100

1.1

PrimateAI

Pathogenic

0.80

Sift4G

Benign

0.49

T;T

Vest4

0.22

MVP

0.072

ClinPred

0.75

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.14

Mutation Taster

=94/6

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over