17-62681986-A-G

Variant names:

• chr17-62681986-A-G
• rs2460300
• NM_006039.5:c.2803+49A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• cardiac rhythm disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006039.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRC2	NM_006039.5	MANE Select	c.2803+49A>G		intron	N/A	NP_006030.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRC2	ENST00000303375.10	TSL:1 MANE Select	c.2803+49A>G		intron	N/A	ENSP00000307513.5
	MRC2	ENST00000583597.5	TSL:1	n.499+49A>G		intron	N/A
	MRC2	ENST00000446119.2	TSL:2	c.-540+49A>G		intron	N/A	ENSP00000400445.2

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

GnomAD2 exomes AF: 0.940 AC: 202291 AN: 215192 AF XY: 0.943

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 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

African (AFR) AF: 0.599 AC: 18462 AN: 30814

American (AMR) AF: 0.968 AC: 37206 AN: 38448

Ashkenazi Jewish (ASJ) AF: 0.984 AC: 24207 AN: 24594

East Asian (EAS) AF: 0.952 AC: 36649 AN: 38498

South Asian (SAS) AF: 0.871 AC: 69875 AN: 80238

European-Finnish (FIN) AF: 0.992 AC: 51618 AN: 52048

Middle Eastern (MID) AF: 0.952 AC: 5274 AN: 5538

European-Non Finnish (NFE) AF: 0.985 AC: 1021984 AN: 1037850

Other (OTH) AF: 0.949 AC: 54055 AN: 56976

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

African (AFR) AF: 0.609 AC: 25202 AN: 41384

American (AMR) AF: 0.942 AC: 14400 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 3417 AN: 3470

East Asian (EAS) AF: 0.936 AC: 4831 AN: 5160

South Asian (SAS) AF: 0.872 AC: 4206 AN: 4824

European-Finnish (FIN) AF: 0.990 AC: 10513 AN: 10614

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.984 AC: 66886 AN: 67976

Other (OTH) AF: 0.903 AC: 1906 AN: 2110

Alfa AF: 0.950 Hom.: 87033

Bravo AF: 0.860

Asia WGS AF: 0.848 AC: 2951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.3
DANN	Benign	0.76
PhyloP100		-0.044
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2460300; hg19: chr17-60759347;