Genetic Variant MSL2:p.Ser540Asn (chr3-136151262-C-T) – 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_018133.4(MSL2):c.1619G>A(p.Ser540Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00758 in 1,614,226 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0063 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0077 ( 61 hom. )

Consequence

MSL2
NM_018133.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.18

Publications

7 publications found

Variant links:

Genes affected

MSL2 (HGNC:25544): (MSL complex subunit 2) Predicted to enable ubiquitin protein ligase activity. Involved in histone H4-K16 acetylation. Part of MSL complex. [provided by Alliance of Genome Resources, Apr 2022]

MSL2 Gene-Disease associations (from GenCC):

Karayol-Borroto-Haghshenas neurodevelopmental syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
complex neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

MSL2 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=0.0052244663).

BP6

Variant 3-136151262-C-T is Benign according to our data. Variant chr3-136151262-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3770473.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 962 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018133.4. 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
	MSL2	NM_018133.4	MANE Select	c.1619G>A	p.Ser540Asn	missense	Exon 2 of 2	NP_060603.2
	MSL2	NM_001145417.2		c.1397G>A	p.Ser466Asn	missense	Exon 2 of 2	NP_001138889.1	Q9HCI7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSL2	ENST00000309993.3	TSL:1 MANE Select	c.1619G>A	p.Ser540Asn	missense	Exon 2 of 2	ENSP00000311827.2	Q9HCI7-1
MSL2	ENST00000703105.1		c.1607G>A	p.Ser536Asn	missense	Exon 2 of 2	ENSP00000515172.1	A0A8V8TR57
MSL2	ENST00000434835.2	TSL:2	c.1397G>A	p.Ser466Asn	missense	Exon 2 of 2	ENSP00000387948.2	Q9HCI7-2

Frequencies

GnomAD3 genomes

AF:

0.00632

AC:

962

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0140

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00899

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00562

AC:

1413

AN:

251398

AF XY:

0.00564

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.00766

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00771

AC:

11268

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00766

AC XY:

5571

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33480

American (AMR)

AF:

0.00148

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00264

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00365

AC:

315

AN:

86258

European-Finnish (FIN)

AF:

0.0142

AC:

761

AN:

53420

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00865

AC:

9615

AN:

1112008

Other (OTH)

AF:

0.00646

AC:

390

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

694

1389

2083

2778

3472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

368

736

1104

1472

1840

<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:

0.00631

AC:

962

AN:

152336

Hom.:

Cov.:

AF XY:

0.00604

AC XY:

450

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

41580

American (AMR)

AF:

0.00327

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00331

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0140

AC:

148

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00899

AC:

612

AN:

68038

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

149

198

248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00676

Hom.:

Bravo

AF:

0.00565

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00872

AC:

ExAC

AF:

0.00549

AC:

666

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00747

EpiControl

AF:

0.00848

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.0

PhyloP100

5.2

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.99

REVEL

Benign

0.091

Sift

Uncertain

0.022

Sift4G

Benign

0.18

Polyphen

0.88

Vest4

0.28

MVP

0.17

MPC

0.46

ClinPred

0.022

GERP RS

5.9

Varity_R

0.16

gMVP

0.69

Mutation Taster

=97/3

polymorphism

(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

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