Genetic Variant MROH2B:c.2241+8_2241+9insAAA (chr5-41033829-C-CTTT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173489.5(MROH2B):c.2241+8_2241+9insAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000226 in 1,324,896 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000014 ( 1 hom., cov: 0)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

MROH2B
NM_173489.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.238

Publications

3 publications found

Variant links:

Genes affected

MROH2B (HGNC:26857): (maestro heat like repeat family member 2B) Predicted to be involved in protein kinase A signaling. Predicted to be located in acrosomal vesicle and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

MROH2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173489.5. 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
	MROH2B	NM_173489.5	MANE Select	c.2241+8_2241+9insAAA		splice_region intron	N/A	NP_775760.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MROH2B	ENST00000399564.5	TSL:1 MANE Select	c.2241+8_2241+9insAAA	splice_region intron	N/A	ENSP00000382476.4	Q7Z745-1
MROH2B	ENST00000506092.6	TSL:2	c.906+8_906+9insAAA	splice_region intron	N/A	ENSP00000441504.1	F5GZ06
MROH2B	ENST00000503890.5	TSL:2	n.1203+8_1203+9insAAA	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

146062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000437

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.48e-7

AC:

AN:

1178834

Hom.:

Cov.:

AF XY:

0.00000170

AC XY:

AN XY:

586890

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27640

American (AMR)

AF:

0.00

AC:

AN:

32796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22206

East Asian (EAS)

AF:

0.00

AC:

AN:

34806

South Asian (SAS)

AF:

0.0000141

AC:

AN:

70752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5122

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

887732

Other (OTH)

AF:

0.00

AC:

AN:

50398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000137

AC:

AN:

146062

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

71180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38830

American (AMR)

AF:

0.00

AC:

AN:

14658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3336

East Asian (EAS)

AF:

0.00

AC:

AN:

5058

South Asian (SAS)

AF:

0.000437

AC:

AN:

4578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66360

Other (OTH)

AF:

0.00

AC:

AN:

1988

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.24

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over