Genetic Variant NM_015026.3:c.1909G>A (chr12-62537159-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015026.3(MON2):c.1909G>A(p.Val637Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,604,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

MON2
NM_015026.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.35

Publications

2 publications found

Variant links:

Genes affected

MON2 (HGNC:29177): (MON2 homolog, regulator of endosome-to-Golgi trafficking) Predicted to be involved in Golgi to endosome transport. Located in early endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

MON2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048173517).

BP6

Variant 12-62537159-G-A is Benign according to our data. Variant chr12-62537159-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2508794.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015026.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MON2	NM_015026.3	MANE Select	c.1909G>A	p.Val637Ile	missense	Exon 15 of 35	NP_055841.2	Q7Z3U7-1
MON2	NM_001278470.2		c.1909G>A	p.Val637Ile	missense	Exon 15 of 34	NP_001265399.1	Q7Z3U7-5
MON2	NM_001278471.2		c.1840G>A	p.Val614Ile	missense	Exon 15 of 34	NP_001265400.1	Q7Z3U7-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MON2	ENST00000393630.8	TSL:1 MANE Select	c.1909G>A	p.Val637Ile	missense	Exon 15 of 35	ENSP00000377250.4	Q7Z3U7-1
MON2	ENST00000393629.6	TSL:1	c.1909G>A	p.Val637Ile	missense	Exon 15 of 34	ENSP00000377249.2	Q7Z3U7-5
MON2	ENST00000552738.5	TSL:1	c.1840G>A	p.Val614Ile	missense	Exon 15 of 34	ENSP00000449215.1	Q7Z3U7-6

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000524

AC:

AN:

248294

AF XY:

0.0000372

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000589

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000978

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000116

AC:

169

AN:

1451992

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

722650

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33178

American (AMR)

AF:

0.0000454

AC:

AN:

44056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25976

East Asian (EAS)

AF:

0.00

AC:

AN:

39364

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84998

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.000146

AC:

161

AN:

1105520

Other (OTH)

AF:

0.0000667

AC:

AN:

59970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000723

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41520

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000193

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0089

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.83

M_CAP

Benign

0.019

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

PhyloP100

7.3

PrimateAI

Benign

0.29

PROVEAN

Benign

0.13

REVEL

Benign

0.13

Sift

Benign

0.70

Sift4G

Benign

0.59

Vest4

0.10

MVP

0.068

ClinPred

0.14

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.040

gMVP

0.043

Mutation Taster

=92/8

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over