17-62681986-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006039.5(MRC2):​c.2803+49A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRC2	NM_006039.5	c.2803+49A>T		intron_variant	Intron 19 of 29	ENST00000303375.10	NP_006030.2
MRC2	XM_011525543.2	c.2803+49A>T		intron_variant	Intron 19 of 23		XP_011523845.1
MRC2	XM_047437208.1	c.2803+49A>T		intron_variant	Intron 19 of 24		XP_047293164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRC2	ENST00000303375.10	c.2803+49A>T		intron_variant	Intron 19 of 29	1	NM_006039.5	ENSP00000307513.5
MRC2	ENST00000583597.5	n.499+49A>T		intron_variant	Intron 3 of 13	1
MRC2	ENST00000446119.2	c.-540+49A>T		intron_variant	Intron 1 of 10	2		ENSP00000400445.2
MRC2	ENST00000579432.1	c.16+49A>T		intron_variant	Intron 1 of 1	4		ENSP00000463968.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1365324 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 680194

African (AFR) AF: 0.00 AC: 0 AN: 30876

American (AMR) AF: 0.00 AC: 0 AN: 38458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24596

East Asian (EAS) AF: 0.00 AC: 0 AN: 38506

South Asian (SAS) AF: 0.00 AC: 0 AN: 80320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5538

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1037990

Other (OTH) AF: 0.00 AC: 0 AN: 56992

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 87033

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.82
PhyloP100		-0.044

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;