Genetic Variant NM_001394639.1:c.2857C>T (chr2-233816781-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_001394639.1(MROH2A):c.2857C>T(p.Leu953Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00593 in 1,549,136 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 47 hom. )

Consequence

MROH2A
NM_001394639.1 missense, splice_region

Scores

Splicing: ADA: 0.04364

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.36

Publications

1 publications found

Variant links:

Genes affected

MROH2A (HGNC:27936): (maestro heat like repeat family member 2A) This gene encodes a HEAT-domain-containing protein. The function of the encoded protein has not been characterized. [provided by RefSeq, Aug 2016]

MROH2A 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=0.005459279).

BP6

Variant 2-233816781-C-T is Benign according to our data. Variant chr2-233816781-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2652026.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394639.1. 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
	MROH2A	NM_001394639.1	MANE Select	c.2857C>T	p.Leu953Phe	missense splice_region	Exon 27 of 42	NP_001381568.1	A6NES4
	MROH2A	NM_001367507.1		c.2857C>T	p.Leu953Phe	missense splice_region	Exon 27 of 42	NP_001354436.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MROH2A	ENST00000389758.4	TSL:5 MANE Select	c.2857C>T	p.Leu953Phe	missense splice_region	Exon 27 of 42	ENSP00000374408.3	A6NES4
	MROH2A	ENST00000610772.4	TSL:5	c.2866C>T	p.Leu956Phe	missense splice_region	Exon 27 of 42	ENSP00000477597.1	A0A087WT58

Frequencies

GnomAD3 genomes

AF:

0.00434

AC:

661

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00641

Gnomad OTH

AF:

0.00432

GnomAD2 exomes

AF:

0.00419

AC:

623

AN:

148748

AF XY:

0.00419

show subpopulations

Gnomad AFR exome

AF:

0.00118

Gnomad AMR exome

AF:

0.00175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00984

Gnomad NFE exome

AF:

0.00696

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00611

AC:

8529

AN:

1396792

Hom.:

Cov.:

AF XY:

0.00581

AC XY:

4004

AN XY:

688986

show subpopulations

African (AFR)

AF:

0.000728

AC:

AN:

31572

American (AMR)

AF:

0.00190

AC:

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.0000795

AC:

AN:

25168

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.000480

AC:

AN:

79192

European-Finnish (FIN)

AF:

0.00789

AC:

380

AN:

48160

Middle Eastern (MID)

AF:

0.00287

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

0.00716

AC:

7717

AN:

1077760

Other (OTH)

AF:

0.00492

AC:

285

AN:

57928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

365

730

1095

1460

1825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.00434

AC:

661

AN:

152344

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

321

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

41572

American (AMR)

AF:

0.00340

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0107

AC:

114

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00641

AC:

436

AN:

68044

Other (OTH)

AF:

0.00427

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

104

139

174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00470

Hom.:

Bravo

AF:

0.00381

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00701

AC:

ExAC

AF:

0.00221

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

0.15

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0082

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.74

PhyloP100

1.4

PROVEAN

Benign

-0.49

REVEL

Benign

0.12

Sift

Benign

0.12

Sift4G

Uncertain

0.028

Vest4

0.21

MVP

0.53

MPC

0.00025

ClinPred

0.018

GERP RS

3.4

Varity_R

0.038

gMVP

0.29

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.044

dbscSNV1_RF

Benign

0.17

SpliceAI score (max)

0.13

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