10-52770876-A-G

Variant names:

• chr10-52770876-A-G
• rs1982266
• NM_001378373.1:c.188-90T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378373.1(MBL2):​c.188-90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 655,040 control chromosomes in the GnomAD database, including 100,694 homozygotes. 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: 𝑓 0.49 (20063 hom., cov: 33)
  • Exomes 𝑓: 0.56 (80631 hom.)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBL2	NM_001378373.1	c.188-90T>C		intron_variant	Intron 2 of 4	ENST00000674931.1	NP_001365302.1
MBL2	NM_000242.3	c.188-90T>C		intron_variant	Intron 1 of 3		NP_000233.1
MBL2	NM_001378374.1	c.188-90T>C		intron_variant	Intron 2 of 4		NP_001365303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBL2	ENST00000674931.1	c.188-90T>C		intron_variant	Intron 2 of 4		NM_001378373.1	ENSP00000502789.1
MBL2	ENST00000373968.3	c.188-90T>C		intron_variant	Intron 1 of 3	1		ENSP00000363079.3
MBL2	ENST00000675947.1	c.188-90T>C		intron_variant	Intron 2 of 4			ENSP00000502615.1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75153 AN: 151964 Hom.: 20037 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.512

GnomAD4 exome AF: 0.561 AC: 282109 AN: 502958 Hom.: 80631 AF XY: 0.559 AC XY: 144059 AN XY: 257632

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.716

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.671

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.622

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.554

GnomAD4 genome AF: 0.495 AC: 75215 AN: 152082 Hom.: 20063 Cov.: 33 AF XY: 0.502 AC XY: 37286 AN XY: 74326

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.517

Alfa AF: 0.552 Hom.: 36568

Bravo AF: 0.491

Asia WGS AF: 0.594 AC: 2065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.9
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs1982266; hg19: chr10-54530636;