17-62666126-A-G

Position:

• chr17-62666126-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006039.5(MRC2):​c.553A>G​(p.Lys185Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRC2 NM_006039.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69

Genes affected

MRC2 (HGNC:16875): (mannose receptor C type 2) This gene encodes a member of the mannose receptor family of proteins that contain a fibronectin type II domain and multiple C-type lectin-like domains. The encoded protein plays a role in extracellular matrix remodeling by mediating the internalization and lysosomal degradation of collagen ligands. Expression of this gene may play a role in the tumorigenesis and metastasis of several malignancies including breast cancer, gliomas and metastatic bone disease. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27681023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRC2	NM_006039.5	c.553A>G	p.Lys185Glu	missense_variant	3/30	ENST00000303375.10	NP_006030.2
MRC2	XM_011525543.2	c.553A>G	p.Lys185Glu	missense_variant	3/24		XP_011523845.1
MRC2	XM_047437208.1	c.553A>G	p.Lys185Glu	missense_variant	3/25		XP_047293164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRC2	ENST00000303375.10	c.553A>G	p.Lys185Glu	missense_variant	3/30	1	NM_006039.5	ENSP00000307513	P1
MRC2	ENST00000584265.1	n.671A>G		non_coding_transcript_exon_variant	3/11	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.553A>G (p.K185E) alteration is located in exon 3 (coding exon 3) of the MRC2 gene. This alteration results from a A to G substitution at nucleotide position 553, causing the lysine (K) at amino acid position 185 to be replaced by a glutamic acid (E). 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	Pathogenic	0.76
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	0.53	D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.14
Sift	Benign	0.81	T
Sift4G	Uncertain	0.036	D
Polyphen		0.74	P
Vest4		0.57
MutPred		0.65		Loss of methylation at K185 (P = 0.0119);
MVP		0.19
MPC		0.59
ClinPred		0.91	D
GERP RS		4.7
Varity_R		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-60743487;