rs55902142

Positions:

• chr10-52770671-C-G
• chr10-52770671-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001378373.1(MBL2):​c.303G>C​(p.Pro101=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000076 in 1,315,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: MBL2 NM_001378373.1 splice_region, synonymous
• Scores: Splicing: ADA: 0.00007633
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.089 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.303G>C	p.Pro101=	splice_region_variant, synonymous_variant	3/5	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3	c.303G>C	p.Pro101=	splice_region_variant, synonymous_variant	2/4		NP_000233.1
MBL2	NM_001378374.1	c.303G>C	p.Pro101=	splice_region_variant, synonymous_variant	3/5		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.303G>C	p.Pro101=	splice_region_variant, synonymous_variant	3/5		NM_001378373.1	ENSP00000502789	P1
MBL2	ENST00000373968.3	c.303G>C	p.Pro101=	splice_region_variant, synonymous_variant	2/4	1		ENSP00000363079	P1
MBL2	ENST00000675947.1	c.303G>C	p.Pro101=	splice_region_variant, synonymous_variant	3/5			ENSP00000502615	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.60e-7 AC: 1 AN: 1315206 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 649974

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.68e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000076
dbscSNV1_RF	Benign	0.0
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: rs55902142; hg19: chr10-54530431;