Variant 22-20425548-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182895.5(SCARF2):c.2428G>A(p.Ala810Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000841 in 1,189,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.4e-7 ( 0 hom. )

Consequence

SCARF2
NM_182895.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09658483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARF2	NM_182895.5 link	c.2428G>A	p.Ala810Thr	missense_variant	11/11	ENST00000622235.5	NP_878315.2	Q96GP6-2
SCARF2	NM_153334.7 link	c.2443G>A	p.Ala815Thr	missense_variant	11/11		NP_699165.3	Q96GP6-1
SCARF2	XM_047441585.1 link	c.2542G>A	p.Ala848Thr	missense_variant	11/11		XP_047297541.1
SCARF2	XM_017029065.3 link	c.*657G>A		3_prime_UTR_variant	11/11		XP_016884554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARF2	ENST00000622235.5 link	c.2428G>A	p.Ala810Thr	missense_variant	11/11	1	NM_182895.5	ENSP00000477564.2		Q96GP6-2
SCARF2	ENST00000623402.1 link	c.2443G>A	p.Ala815Thr	missense_variant	11/11	1		ENSP00000485276.1		Q96GP6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.41e-7

AC:

AN:

1189250

Hom.:

Cov.:

AF XY:

0.00000174

AC XY:

AN XY:

575526

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000102

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.2440G>A (p.A814T) 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 2440, causing the alanine (A) at amino acid position 814 to be replaced by a threonine (T). 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

0.068

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.5

DANN

Benign

0.84

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.45

T;T

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.097

T;T

MetaSVM

Benign

-0.97

PrimateAI

Pathogenic

0.80

Sift4G

Benign

1.0

T;T

Vest4

0.072

MVP

0.092

ClinPred

0.048

GERP RS

0.078

Varity_R

0.019

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over