dbSNP rs1266479: MAN2A2:n.*2419C>T (chr15-90921602-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000560451.6(MAN2A2):n.*2419C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,180 control chromosomes in the GnomAD database, including 2,472 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 0.14 ( 2472 hom., cov: 33)

Exomes 𝑓: 0.17 ( 0 hom. )

Consequence

MAN2A2
ENST00000560451.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.360

Publications

7 publications found

Variant links:

Genes affected

MAN2A2 (HGNC:6825): (mannosidase alpha class 2A member 2) Predicted to enable alpha-mannosidase activity. Predicted to be involved in N-glycan processing and protein deglycosylation. Predicted to be integral component of membrane. Predicted to be active in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

MAN2A2 Gene-Disease associations (from GenCC):

disorder of glycosylation
Inheritance: AR Classification: LIMITED Submitted by: G2P

MAN2A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN2A2	NM_006122.4 link	c.*1815C>T		3_prime_UTR_variant	Exon 23 of 23	ENST00000559717.6	NP_006113.2	P49641-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAN2A2	ENST00000560451.6 link	n.*2419C>T	non_coding_transcript_exon_variant	Exon 23 of 23	1		ENSP00000453999.1	H0YNG5
MAN2A2	ENST00000559717.6 link	c.*1815C>T	3_prime_UTR_variant	Exon 23 of 23	2	NM_006122.4	ENSP00000452948.1	P49641-3
MAN2A2	ENST00000360468.7 link	c.*1815C>T	3_prime_UTR_variant	Exon 22 of 22	1		ENSP00000353655.3	P49641-3
MAN2A2	ENST00000560451.6 link	n.*2419C>T	3_prime_UTR_variant	Exon 23 of 23	1		ENSP00000453999.1	H0YNG5

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21970

AN:

152056

Hom.:

2462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0749

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.0952

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0794

Gnomad OTH

AF:

0.126

GnomAD4 exome

AF:

0.167

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.145

AC:

22013

AN:

152174

Hom.:

2472

Cov.:

AF XY:

0.143

AC XY:

10669

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.310

AC:

12849

AN:

41458

American (AMR)

AF:

0.0748

AC:

1144

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

445

AN:

3472

East Asian (EAS)

AF:

0.00231

AC:

AN:

5194

South Asian (SAS)

AF:

0.155

AC:

748

AN:

4824

European-Finnish (FIN)

AF:

0.0952

AC:

1009

AN:

10602

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0794

AC:

5401

AN:

68018

Other (OTH)

AF:

0.125

AC:

264

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

860

1720

2580

3440

4300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.103

Hom.:

1528

Bravo

AF:

0.149

Asia WGS

AF:

0.108

AC:

375

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

3.5

(source)

DANN

Benign

0.75

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over