Variant chr17-62664893-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006039.5(MRC2):c.464G>C(p.Ser155Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00133 in 1,613,350 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 13 hom. )

Consequence

MRC2
NM_006039.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043460727).

BP6

Variant 17-62664893-G-C is Benign according to our data. Variant chr17-62664893-G-C is described in ClinVar as [Benign]. Clinvar id is 778720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00661 (1007/152354) while in subpopulation AFR AF= 0.0227 (946/41592). AF 95% confidence interval is 0.0215. There are 10 homozygotes in gnomad4. There are 470 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRC2	NM_006039.5 link	c.464G>C	p.Ser155Thr	missense_variant	2/30	ENST00000303375.10	NP_006030.2	Q9UBG0
MRC2	XM_011525543.2 link	c.464G>C	p.Ser155Thr	missense_variant	2/24		XP_011523845.1
MRC2	XM_047437208.1 link	c.464G>C	p.Ser155Thr	missense_variant	2/25		XP_047293164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRC2	ENST00000303375.10 link	c.464G>C	p.Ser155Thr	missense_variant	2/30	1	NM_006039.5	ENSP00000307513.5		Q9UBG0
MRC2	ENST00000584265.1 link	n.582G>C		non_coding_transcript_exon_variant	2/11	5

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

988

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00179

AC:

448

AN:

250068

Hom.:

AF XY:

0.00118

AC XY:

160

AN XY:

135348

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000974

Gnomad OTH exome

AF:

0.000984

GnomAD4 exome

AF:

0.000780

AC:

1139

AN:

1460996

Hom.:

Cov.:

AF XY:

0.000622

AC XY:

452

AN XY:

726830

show subpopulations

Gnomad4 AFR exome

AF:

0.0260

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.00212

GnomAD4 genome

AF:

0.00661

AC:

1007

AN:

152354

Hom.:

Cov.:

AF XY:

0.00631

AC XY:

470

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0227

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00225

Hom.:

Bravo

AF:

0.00761

ESP6500AA

AF:

0.0200

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00203

AC:

246

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.14

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.098

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.8

REVEL

Benign

0.081

Sift

Benign

0.36

Sift4G

Benign

0.14

Polyphen

0.19

Vest4

0.19

MVP

0.41

MPC

0.38

ClinPred

0.020

GERP RS

4.3

Varity_R

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over