10-52771925-G-C

Position:

• chr10-52771925-G-C

Variant summary

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

The NM_001378373.1(MBL2):​c.-9-281C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,126 control chromosomes in the GnomAD database, including 50,206 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 0.81 (50206 hom., cov: 32)
• Consequence: MBL2 NM_001378373.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBL2	NM_001378373.1	c.-9-281C>G		intron_variant		ENST00000674931.1
MBL2	NM_001378374.1	c.-24-266C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBL2	ENST00000674931.1	c.-9-281C>G		intron_variant			NM_001378373.1	P1
MBL2	ENST00000675947.1	c.-24-266C>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123347 AN: 152008 Hom.: 50149 Cov.: 32

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.804

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.812 AC: 123464 AN: 152126 Hom.: 50206 Cov.: 32 AF XY: 0.814 AC XY: 60556 AN XY: 74368

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.868

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.806

Alfa AF: 0.711 Hom.: 2029

Bravo AF: 0.823

Asia WGS AF: 0.807 AC: 2807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7096206; hg19: chr10-54531685;