10-52770671-C-A

Variant names:

• chr10-52770671-C-A
• rs55902142
• NM_001378373.1:c.303G>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.303G>T​(p.Pro101Pro) 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. Synonymous variant affecting the same amino acid position (i.e. P101P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: MBL2 NM_001378373.1 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001385
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 0 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=-0.83).
• BP7: Synonymous conserved (PhyloP=0.089 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378373.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	NM_001378373.1	MANE Select	c.303G>T	p.Pro101Pro	splice_region synonymous	Exon 3 of 5	NP_001365302.1	P11226
	MBL2	NM_000242.3		c.303G>T	p.Pro101Pro	splice_region synonymous	Exon 2 of 4	NP_000233.1	P11226
	MBL2	NM_001378374.1		c.303G>T	p.Pro101Pro	splice_region synonymous	Exon 3 of 5	NP_001365303.1	P11226

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	ENST00000674931.1	MANE Select	c.303G>T	p.Pro101Pro	splice_region synonymous	Exon 3 of 5	ENSP00000502789.1	P11226
	MBL2	ENST00000373968.3	TSL:1	c.303G>T	p.Pro101Pro	splice_region synonymous	Exon 2 of 4	ENSP00000363079.3	P11226
	MBL2	ENST00000675947.1		c.303G>T	p.Pro101Pro	splice_region synonymous	Exon 3 of 5	ENSP00000502615.1	P11226

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.60e-7 AC: 1 AN: 1315206 Hom.: 0 Cov.: 30 AF XY: 0.00000154 AC XY: 1 AN XY: 649974

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27884

American (AMR) AF: 0.00 AC: 0 AN: 29738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20552

East Asian (EAS) AF: 0.00 AC: 0 AN: 33828

South Asian (SAS) AF: 0.0000159 AC: 1 AN: 62940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5118

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1033474

Other (OTH) AF: 0.00 AC: 0 AN: 52782

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.29
PhyloP100		0.089

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.0080
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: rs55902142; hg19: chr10-54530431;