10-52768506-G-A

Variant names:

• chr10-52768506-G-A
• rs930507
• NM_001378373.1:c.378C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001378373.1(MBL2):​c.378C>T​(p.Leu126Leu) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. L126L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MBL2 NM_001378373.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 45 publications found

Genes affected

MBL2 (HGNC:6922): (mannose binding lectin 2) This gene encodes the soluble mannose-binding lectin or mannose-binding protein found in serum. The protein encoded belongs to the collectin family and is an important element in the innate immune system. The protein recognizes and binds to mannose and N-acetylglucosamine on many microorganisms, including bacteria, yeast, and viruses including influenza virus, HIV and SARS-CoV. This binding activates the classical complement pathway. Deficiencies of this gene have been associated with susceptibility to autoimmune and infectious diseases. [provided by RefSeq, Jun 2020]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-1.68 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.378C>T	p.Leu126Leu	synonymous_variant	Exon 5 of 5	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3	c.378C>T	p.Leu126Leu	synonymous_variant	Exon 4 of 4		NP_000233.1
MBL2	NM_001378374.1	c.378C>T	p.Leu126Leu	synonymous_variant	Exon 5 of 5		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.378C>T	p.Leu126Leu	synonymous_variant	Exon 5 of 5		NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000373968.3	c.378C>T	p.Leu126Leu	synonymous_variant	Exon 4 of 4	1		ENSP00000363079.3
MBL2	ENST00000675947.1	c.378C>T	p.Leu126Leu	synonymous_variant	Exon 5 of 5			ENSP00000502615.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1404032 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 693070

African (AFR) AF: 0.00 AC: 0 AN: 31514

American (AMR) AF: 0.00 AC: 0 AN: 36684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21970

East Asian (EAS) AF: 0.00 AC: 0 AN: 39294

South Asian (SAS) AF: 0.00 AC: 0 AN: 74722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5448

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085356

Other (OTH) AF: 0.00 AC: 0 AN: 57896

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 8696

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.0
DANN	Benign	0.86
PhyloP100		-1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs930507; hg19: chr10-54528266;