Variant chr17-62666568-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006039.5(MRC2):c.808G>C(p.Gly270Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MRC2
NM_006039.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.89

Variant links:

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]

MRC2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.845

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRC2	NM_006039.5 link	c.808G>C	p.Gly270Arg	missense_variant	4/30	ENST00000303375.10	NP_006030.2	Q9UBG0
MRC2	XM_011525543.2 link	c.808G>C	p.Gly270Arg	missense_variant	4/24		XP_011523845.1
MRC2	XM_047437208.1 link	c.808G>C	p.Gly270Arg	missense_variant	4/25		XP_047293164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRC2	ENST00000303375.10 link	c.808G>C	p.Gly270Arg	missense_variant	4/30	1	NM_006039.5	ENSP00000307513.5		Q9UBG0
MRC2	ENST00000584265.1 link	n.926G>C		non_coding_transcript_exon_variant	4/11	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725562

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:

0.00000180

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

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2024

The c.808G>C (p.G270R) alteration is located in exon 4 (coding exon 4) of the MRC2 gene. This alteration results from a G to C substitution at nucleotide position 808, causing the glycine (G) at amino acid position 270 to be replaced by an arginine (R). 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

Uncertain

0.45

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.065

MetaRNN

Pathogenic

0.84

MetaSVM

Benign

-0.49

MutationAssessor

Pathogenic

2.9

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-4.2

REVEL

Uncertain

0.49

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.74

MutPred

0.71

Gain of solvent accessibility (P = 0.0171);

MVP

0.35

MPC

1.3

ClinPred

0.99

GERP RS

4.0

Varity_R

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

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

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