Variant 2-233816781-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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

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 made for transcript

Verdict is Benign. Variant got -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 id is 2652026.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH2A	NM_001394639.1 linkuse as main transcript	c.2857C>T	p.Leu953Phe	missense_variant, splice_region_variant	27/42	ENST00000389758.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH2A	ENST00000389758.4 linkuse as main transcript	c.2857C>T	p.Leu953Phe	missense_variant, splice_region_variant	27/42	5	NM_001394639.1	A2
MROH2A	ENST00000610772.4 linkuse as main transcript	c.2866C>T	p.Leu956Phe	missense_variant, splice_region_variant	27/42	5		P4

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

GnomAD3 exomes

AF:

0.00419

AC:

623

AN:

148748

Hom.:

AF XY:

0.00419

AC XY:

336

AN XY:

80136

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 SAS exome

AF:

0.000355

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

Gnomad4 AFR exome

AF:

0.000728

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.0000795

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000480

Gnomad4 FIN exome

AF:

0.00789

Gnomad4 NFE exome

AF:

0.00716

Gnomad4 OTH exome

AF:

0.00492

GnomAD4 genome

AF:

0.00434

AC:

661

AN:

152344

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

321

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.00641

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00536

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

MROH2A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-0.74

MutationTaster

Benign

0.91

Sift4G

Uncertain

0.028

D;D

Vest4

0.21

MVP

0.53

MPC

.;2.46197207718E-4

ClinPred

0.018

GERP RS

3.4

Varity_R

0.038

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over