chr2-233794419-C-G

Variant names:

• chr2-233794419-C-G
• rs187531871
• NM_001394639.1:c.879C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001394639.1(MROH2A):​c.879C>G​(p.Asn293Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N293N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MROH2A NM_001394639.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.879C>G	p.Asn293Lys	missense	Exon 8 of 42	NP_001381568.1	A6NES4
	MROH2A	NM_001367507.1		c.879C>G	p.Asn293Lys	missense	Exon 8 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.879C>G	p.Asn293Lys	missense	Exon 8 of 42	ENSP00000374408.3	A6NES4
	MROH2A	ENST00000610772.4	TSL:5	c.879C>G	p.Asn293Lys	missense	Exon 8 of 42	ENSP00000477597.1	A0A087WT58

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.2
DANN	Benign	0.95
DEOGEN2	Benign	0.00033	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.86	T
PhyloP100		-0.72
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Benign	0.23	T
Sift4G	Benign	0.13	T
Vest4		0.23
MutPred		0.57		Gain of ubiquitination at N293 (P = 0.0146)
MVP		0.081
MPC		0.00025
ClinPred		0.12	T
GERP RS		-2.7
Varity_R		0.032
gMVP		0.095
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.71		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.71		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs187531871; hg19: chr2-234703065;