rs4663335

Positions:

• chr2-233780444-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394639.1(MROH2A):​c.276+592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,194 control chromosomes in the GnomAD database, including 1,824 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1824 hom., cov: 32)
• Consequence: MROH2A NM_001394639.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MROH2A	NM_001394639.1	c.276+592G>A		intron_variant		ENST00000389758.4	NP_001381568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MROH2A	ENST00000389758.4	c.276+592G>A		intron_variant		5	NM_001394639.1	ENSP00000374408	A2
MROH2A	ENST00000610772.4	c.276+592G>A		intron_variant		5		ENSP00000477597	P4
MROH2A	ENST00000480634.2	n.182+592G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22856 AN: 152076 Hom.: 1815 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.159

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.150 AC: 22896 AN: 152194 Hom.: 1824 Cov.: 32 AF XY: 0.152 AC XY: 11291 AN XY: 74416

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.163

Alfa AF: 0.151 Hom.: 2600

Bravo AF: 0.148

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
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: rs4663335; hg19: chr2-234689090;