17-62681986-A-G

Position:

• chr17-62681986-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006039.5(MRC2):​c.2803+49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.957 in 1,517,036 control chromosomes in the GnomAD database, including 700,320 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.87 (59845 hom., cov: 33)
  • Exomes 𝑓: 0.97 (640475 hom.)
• Consequence: MRC2 NM_006039.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRC2	NM_006039.5	c.2803+49A>G		intron_variant		ENST00000303375.10	NP_006030.2
MRC2	XM_011525543.2	c.2803+49A>G		intron_variant			XP_011523845.1
MRC2	XM_047437208.1	c.2803+49A>G		intron_variant			XP_047293164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRC2	ENST00000303375.10	c.2803+49A>G		intron_variant		1	NM_006039.5	ENSP00000307513.5
MRC2	ENST00000583597.5	n.499+49A>G		intron_variant		1
MRC2	ENST00000446119.2	c.-540+49A>G		intron_variant		2		ENSP00000400445.2
MRC2	ENST00000579432.1	c.16+49A>G		intron_variant		4		ENSP00000463968.1

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132472 AN: 151914 Hom.: 59820 Cov.: 33

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.984

Gnomad OTH AF: 0.909

GnomAD3 exomes AF: 0.940 AC: 202291 AN: 215192 Hom.: 96049 AF XY: 0.943 AC XY: 109339 AN XY: 115998

Gnomad AFR exome AF: 0.607

Gnomad AMR exome AF: 0.970

Gnomad ASJ exome AF: 0.984

Gnomad EAS exome AF: 0.932

Gnomad SAS exome AF: 0.865

Gnomad FIN exome AF: 0.991

Gnomad NFE exome AF: 0.984

Gnomad OTH exome AF: 0.964

GnomAD4 exome AF: 0.967 AC: 1319330 AN: 1365004 Hom.: 640475 Cov.: 19 AF XY: 0.965 AC XY: 656188 AN XY: 680016

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.968

Gnomad4 ASJ exome AF: 0.984

Gnomad4 EAS exome AF: 0.952

Gnomad4 SAS exome AF: 0.871

Gnomad4 FIN exome AF: 0.992

Gnomad4 NFE exome AF: 0.985

Gnomad4 OTH exome AF: 0.949

GnomAD4 genome AF: 0.872 AC: 132540 AN: 152032 Hom.: 59845 Cov.: 33 AF XY: 0.874 AC XY: 64992 AN XY: 74356

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.942

Gnomad4 ASJ AF: 0.985

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.990

Gnomad4 NFE AF: 0.984

Gnomad4 OTH AF: 0.903

Alfa AF: 0.967 Hom.: 68168

Bravo AF: 0.860

Asia WGS AF: 0.848 AC: 2951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.3
DANN	Benign	0.76

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

Other links and lift over

dbSNP: rs2460300; hg19: chr17-60759347;