2-118971499-G-A

Position:

• chr2-118971499-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_006770.4(MARCO):​c.425G>A​(p.Gly142Glu) variant causes a missense, splice region 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. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MARCO NM_006770.4 missense, splice_region
• Scores: Splicing: ADA: 0.0003797
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.865

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14922789).
• BP6: Variant 2-118971499-G-A is Benign according to our data. Variant chr2-118971499-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2390086.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARCO	NM_006770.4	c.425G>A	p.Gly142Glu	missense_variant, splice_region_variant	4/17	ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3	c.425G>A	p.Gly142Glu	missense_variant, splice_region_variant	4/17		XP_011510384.1
MARCO	XM_017005171.3	c.425G>A	p.Gly142Glu	missense_variant, splice_region_variant	4/9		XP_016860660.1
MARCO	XM_011512083.4	c.98-2834G>A		intron_variant			XP_011510385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5	c.425G>A	p.Gly142Glu	missense_variant, splice_region_variant	4/17	1	NM_006770.4	ENSP00000318916	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	13
DANN	Benign	0.41
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Pathogenic	3.6	H
MutationTaster	Benign	0.55	D;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.22
Sift	Benign	0.72	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.18
MVP		0.92
MPC		0.13
ClinPred		0.12	T
GERP RS		3.2
Varity_R		0.032
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00038
dbscSNV1_RF	Benign	0.16
SpliceAI score (max)		0.040		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.

Other links and lift over

hg19: chr2-119729075; COSMIC: COSV59051517; COSMIC: COSV59051517;