2-118981487-T-G

Position:

• chr2-118981487-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006770.4(MARCO):​c.845T>G​(p.Phe282Cys) 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 benign outcome for this variant. 15/21 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. F282S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MARCO NM_006770.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

Genes affected

MARCO (HGNC:6895): (macrophage receptor with collagenous structure) The protein encoded by this gene is a member of the class A scavenger receptor family and is part of the innate antimicrobial immune system. The protein may bind both Gram-negative and Gram-positive bacteria via an extracellular, C-terminal, scavenger receptor cysteine-rich (SRCR) domain. In addition to short cytoplasmic and transmembrane domains, there is an extracellular spacer domain and a long, extracellular collagenous domain. The protein may form a trimeric molecule by the association of the collagenous domains of three identical polypeptide chains. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.26104432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCO	NM_006770.4	c.845T>G	p.Phe282Cys	missense_variant	9/17	ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3	c.845T>G	p.Phe282Cys	missense_variant	9/17		XP_011510384.1
MARCO	XM_011512083.4	c.482T>G	p.Phe161Cys	missense_variant	6/14		XP_011510385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5	c.845T>G	p.Phe282Cys	missense_variant	9/17	1	NM_006770.4	ENSP00000318916.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.42
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	-0.084	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.13
Sift	Benign	0.18	T
Sift4G	Benign	0.11	T
Polyphen		0.0040	B
Vest4		0.12
MutPred		0.19		Gain of glycosylation at S278 (P = 0.1201);
MVP		0.69
MPC		0.064
ClinPred		0.097	T
GERP RS		4.5
Varity_R		0.050
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6761637; hg19: chr2-119739063;