10-52771601-A-G

Variant names:

• chr10-52771601-A-G
• rs72661127
• NM_001378373.1:c.35T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001378373.1(MBL2):​c.35T>C​(p.Leu12Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L12R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MBL2 NM_001378373.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21
• Publications: 2 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	NM_001378373.1	MANE Select	c.35T>C	p.Leu12Pro	missense	Exon 2 of 5	NP_001365302.1
	MBL2	NM_000242.3		c.35T>C	p.Leu12Pro	missense	Exon 1 of 4	NP_000233.1
	MBL2	NM_001378374.1		c.35T>C	p.Leu12Pro	missense	Exon 2 of 5	NP_001365303.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBL2	ENST00000674931.1	MANE Select	c.35T>C	p.Leu12Pro	missense	Exon 2 of 5	ENSP00000502789.1
	MBL2	ENST00000373968.3	TSL:1	c.35T>C	p.Leu12Pro	missense	Exon 1 of 4	ENSP00000363079.3
	MBL2	ENST00000675947.1		c.35T>C	p.Leu12Pro	missense	Exon 2 of 5	ENSP00000502615.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.2
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.69		Gain of loop (P = 0.0045)
MVP		0.81
MPC		0.42
ClinPred		0.92	D
GERP RS		3.7
PromoterAI		-0.0038	Neutral
Varity_R		0.78
gMVP		0.63
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs72661127; hg19: chr10-54531361;