10-52765687-T-A

Variant names:

• chr10-52765687-T-A
• rs56325023
• NM_001378373.1:c.*2450A>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001378373.1(MBL2):​c.*2450A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 152,284 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0042 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MBL2 NM_001378373.1 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: 0.214
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 10-52765687-T-A is Benign according to our data. Variant chr10-52765687-T-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 300108.
• BS2: High AC in GnomAd4 at 643 AD gene.

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.*2450A>T		3_prime_UTR	Exon 5 of 5	NP_001365302.1	P11226
	MBL2	NM_000242.3		c.*2450A>T		3_prime_UTR	Exon 4 of 4	NP_000233.1	P11226
	MBL2	NM_001378374.1		c.*2450A>T		3_prime_UTR	Exon 5 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.*2450A>T		3_prime_UTR	Exon 5 of 5	ENSP00000502789.1	P11226
	MBL2	ENST00000373968.3	TSL:1	c.*2450A>T		3_prime_UTR	Exon 4 of 4	ENSP00000363079.3	P11226
	MBL2	ENST00000675947.1		c.*2450A>T		3_prime_UTR	Exon 5 of 5	ENSP00000502615.1	P11226

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 645 AN: 152166 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00607

Gnomad OTH AF: 0.00669

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00422 AC: 643 AN: 152284 Hom.: 6 Cov.: 33 AF XY: 0.00392 AC XY: 292 AN XY: 74454

African (AFR) AF: 0.00118 AC: 49 AN: 41572

American (AMR) AF: 0.00373 AC: 57 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3464

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0108 AC: 52 AN: 4822

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10610

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.00607 AC: 413 AN: 68018

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00455 Hom.: 0

Bravo AF: 0.00435

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)
-	1	-	Mannose-binding lectin deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.92
PhyloP100		0.21
Mutation Taster		=100/0	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: rs56325023; hg19: chr10-54525447;