10-52771815-T-C

Variant names:

• chr10-52771815-T-C
• rs67990116
• NM_001378373.1:c.-9-171A>G

Variant summary

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

The NM_001378373.1(MBL2):​c.-9-171A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000134 in 745,908 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000013 (0 hom.)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.-9-171A>G		intron	N/A	NP_001365302.1	P11226
	MBL2	NM_001378374.1		c.-24-156A>G		intron	N/A	NP_001365303.1	P11226
	MBL2	NM_000242.3		c.-180A>G		upstream_gene	N/A	NP_000233.1	P11226

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	ENST00000674931.1	MANE Select	c.-9-171A>G		intron	N/A	ENSP00000502789.1	P11226
	MBL2	ENST00000675947.1		c.-24-156A>G		intron	N/A	ENSP00000502615.1	P11226
	MBL2	ENST00000877442.1		c.-9-171A>G		intron	N/A	ENSP00000547501.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000134 AC: 1 AN: 745908 Hom.: 0 AF XY: 0.00000266 AC XY: 1 AN XY: 375258

African (AFR) AF: 0.00 AC: 0 AN: 17434

American (AMR) AF: 0.00 AC: 0 AN: 19006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14680

East Asian (EAS) AF: 0.00 AC: 0 AN: 31994

South Asian (SAS) AF: 0.0000212 AC: 1 AN: 47156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2520

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 548624

Other (OTH) AF: 0.00 AC: 0 AN: 35010

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.68
DANN	Benign	0.60
PhyloP100		-0.77
PromoterAI		0.0010	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs67990116; hg19: chr10-54531575;