2-233828701-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001394639.1(MROH2A):c.4185C>T(p.Ala1395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000324 in 1,550,674 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (1 hom.)
• Consequence: MROH2A NM_001394639.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 2-233828701-C-T is Benign according to our data. Variant chr2-233828701-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652027.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MROH2A	NM_001394639.1	c.4185C>T	p.Ala1395=	synonymous_variant	36/42	ENST00000389758.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH2A	ENST00000389758.4	c.4185C>T	p.Ala1395=	synonymous_variant	36/42	5	NM_001394639.1	A2
MROH2A	ENST00000487979.1	n.147C>T		non_coding_transcript_exon_variant	1/7	1
MROH2A	ENST00000610772.4	c.4227C>T	p.Ala1409=	synonymous_variant	36/42	5		P4

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 63 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000422 AC: 63 AN: 149332 Hom.: 0 AF XY: 0.000398 AC XY: 32 AN XY: 80426

Gnomad AFR exome AF: 0.000444

Gnomad AMR exome AF: 0.000285

Gnomad ASJ exome AF: 0.00310

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000133

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000381

Gnomad OTH exome AF: 0.000692

GnomAD4 exome AF: 0.000313 AC: 438 AN: 1398354 Hom.: 1 Cov.: 31 AF XY: 0.000344 AC XY: 237 AN XY: 689700

Gnomad4 AFR exome AF: 0.000665

Gnomad4 AMR exome AF: 0.000364

Gnomad4 ASJ exome AF: 0.00326

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.0000631

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000274

Gnomad4 OTH exome AF: 0.000293

GnomAD4 genome AF: 0.000420 AC: 64 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.000362 AC XY: 27 AN XY: 74486

Gnomad4 AFR AF: 0.000601

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000518 Hom.: 0

Bravo AF: 0.000533

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

MROH2A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.72
Dann	Benign	0.71

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

LitVar

Other links and lift over

dbSNP: rs563807941; hg19: chr2-234737347;