2-233793782-T-C

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.780T>C(p.Tyr260=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,485,982 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 0.00074 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: MROH2A NM_001394639.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.425

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=-0.65).
• BP6: Variant 2-233793782-T-C is Benign according to our data. Variant chr2-233793782-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2652023.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.780T>C	p.Tyr260=	synonymous_variant	7/42	ENST00000389758.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MROH2A	ENST00000389758.4	c.780T>C	p.Tyr260=	synonymous_variant	7/42	5	NM_001394639.1	A2
MROH2A	ENST00000610772.4	c.780T>C	p.Tyr260=	synonymous_variant	7/42	5		P4
MROH2A	ENST00000480634.2	n.292T>C		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.000743 AC: 113 AN: 152154 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000622 AC: 62 AN: 99676 Hom.: 0 AF XY: 0.000519 AC XY: 28 AN XY: 53984

Gnomad AFR exome AF: 0.000269

Gnomad AMR exome AF: 0.000508

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000194

Gnomad NFE exome AF: 0.00138

Gnomad OTH exome AF: 0.000359

GnomAD4 exome AF: 0.00106 AC: 1411 AN: 1333710 Hom.: 1 Cov.: 29 AF XY: 0.00103 AC XY: 674 AN XY: 654794

Gnomad4 AFR exome AF: 0.000210

Gnomad4 AMR exome AF: 0.000320

Gnomad4 ASJ exome AF: 0.000218

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.00129

Gnomad4 OTH exome AF: 0.000668

GnomAD4 genome AF: 0.000742 AC: 113 AN: 152272 Hom.: 0 Cov.: 33 AF XY: 0.000645 AC XY: 48 AN XY: 74464

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000899 Hom.: 0

Bravo AF: 0.000684

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

Jun 01, 2022

MROH2A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	0.26
Dann	Benign	0.33

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: rs537532834; hg19: chr2-234702428;