chr2-118969259-A-G

Variant names:

• chr2-118969259-A-G
• rs781463416
• NM_006770.4:c.197A>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.197A>G​(p.Gln66Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MARCO NM_006770.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001637
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=0.18684775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCO	NM_006770.4	c.197A>G	p.Gln66Arg	missense_variant, splice_region_variant	Exon 2 of 17	ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3	c.197A>G	p.Gln66Arg	missense_variant, splice_region_variant	Exon 2 of 17		XP_011510384.1
MARCO	XM_017005171.3	c.197A>G	p.Gln66Arg	missense_variant, splice_region_variant	Exon 2 of 9		XP_016860660.1
MARCO	XM_011512083.4	c.98-5074A>G		intron_variant	Intron 1 of 13		XP_011510385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5	c.197A>G	p.Gln66Arg	missense_variant, splice_region_variant	Exon 2 of 17	1	NM_006770.4	ENSP00000318916.4
MARCO	ENST00000412481.1	c.-38A>G		splice_region_variant	Exon 3 of 4	4		ENSP00000409192.1
MARCO	ENST00000412481	c.-38A>G		5_prime_UTR_variant	Exon 3 of 4	4		ENSP00000409192.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461514 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727092

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.40
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.21
Sift	Benign	0.037	D
Sift4G	Benign	0.16	T
Polyphen		0.0050	B
Vest4		0.30
MutPred		0.61		Gain of methylation at Q66 (P = 0.0121);
MVP		0.88
MPC		0.059
ClinPred		0.040	T
GERP RS		2.1
Varity_R		0.065
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.030		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: rs781463416; hg19: chr2-119726835;