dbSNP rs2677744: MAN2A2:c.1010-98G>A (chr15-90907211-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006122.4(MAN2A2):c.1010-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,217,344 control chromosomes in the GnomAD database, including 140,358 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 0.55 ( 25605 hom., cov: 34)

Exomes 𝑓: 0.44 ( 114753 hom. )

Consequence

MAN2A2
NM_006122.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.06

Publications

38 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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN2A2	NM_006122.4 link	c.1010-98G>A		intron_variant	Intron 7 of 22	ENST00000559717.6	NP_006113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN2A2	ENST00000559717.6 link	c.1010-98G>A		intron_variant	Intron 7 of 22	2	NM_006122.4	ENSP00000452948.1

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82858

AN:

152006

Hom.:

25558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.775

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.641

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.986

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.376

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.535

GnomAD4 exome

AF:

0.437

AC:

465632

AN:

1065220

Hom.:

114753

Cov.:

AF XY:

0.439

AC XY:

235470

AN XY:

536596

show subpopulations

African (AFR)

AF:

0.789

AC:

20082

AN:

25466

American (AMR)

AF:

0.731

AC:

27711

AN:

37918

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

8236

AN:

19974

East Asian (EAS)

AF:

0.994

AC:

37245

AN:

37464

South Asian (SAS)

AF:

0.593

AC:

41123

AN:

69394

European-Finnish (FIN)

AF:

0.364

AC:

14592

AN:

40084

Middle Eastern (MID)

AF:

0.480

AC:

2318

AN:

4828

European-Non Finnish (NFE)

AF:

0.373

AC:

292278

AN:

783246

Other (OTH)

AF:

0.471

AC:

22047

AN:

46846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

12203

24406

36608

48811

61014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8552

17104

25656

34208

42760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.545

AC:

82961

AN:

152124

Hom.:

25605

Cov.:

AF XY:

0.551

AC XY:

40976

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.775

AC:

32182

AN:

41502

American (AMR)

AF:

0.641

AC:

9812

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1443

AN:

3470

East Asian (EAS)

AF:

0.986

AC:

5112

AN:

5186

South Asian (SAS)

AF:

0.603

AC:

2910

AN:

4824

European-Finnish (FIN)

AF:

0.376

AC:

3988

AN:

10596

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.380

AC:

25841

AN:

67934

Other (OTH)

AF:

0.540

AC:

1140

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1704

3408

5112

6816

8520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<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:

0.477

Hom.:

37242

Bravo

AF:

0.579

Asia WGS

AF:

0.822

AC:

2855

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.054

(source)

DANN

Benign

0.49

PhyloP100

-3.1

PromoterAI

0.027

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over