Genetic Variant MROH2B:c.2241+8_2241+9insAATAAGATAGATA (chr5-41033829-C-CTATCTATCTTATT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_173489.5(MROH2B):c.2241+8_2241+9insAATAAGATAGATA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,324,998 control chromosomes in the GnomAD database, including 4 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00013 ( 4 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MROH2B	NM_173489.5 link	c.2241+8_2241+9insAATAAGATAGATA	splice_region_variant, intron_variant	Intron 22 of 41	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2 link	c.2241+8_2241+9insAATAAGATAGATA	splice_region_variant, intron_variant	Intron 22 of 42		XP_011512254.1
MROH2B	XM_011513953.2 link	c.2055+8_2055+9insAATAAGATAGATA	splice_region_variant, intron_variant	Intron 21 of 40		XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MROH2B	ENST00000399564.5 link	c.2241+8_2241+9insAATAAGATAGATA	splice_region_variant, intron_variant	Intron 22 of 41	1	NM_173489.5	ENSP00000382476.4	Q7Z745-1
MROH2B	ENST00000506092.6 link	c.906+8_906+9insAATAAGATAGATA	splice_region_variant, intron_variant	Intron 12 of 31	2		ENSP00000441504.1	F5GZ06
MROH2B	ENST00000503890.5 link	n.1203+8_1203+9insAATAAGATAGATA	splice_region_variant, intron_variant	Intron 10 of 30	2
MROH2B	ENST00000515297.5 link	n.1629+8_1629+9insAATAAGATAGATA	splice_region_variant, intron_variant	Intron 16 of 35	5

Frequencies

GnomAD3 genomes

AF:

0.000212

AC:

AN:

146062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000750

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:

0.000256

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000128

AC:

151

AN:

1178822

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

AN XY:

586882

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27640

American (AMR)

AF:

0.000488

AC:

AN:

32794

Ashkenazi Jewish (ASJ)

AF:

0.0000901

AC:

AN:

22206

East Asian (EAS)

AF:

0.00

AC:

AN:

34806

South Asian (SAS)

AF:

0.000339

AC:

AN:

70750

European-Finnish (FIN)

AF:

0.0000633

AC:

AN:

47382

Middle Eastern (MID)

AF:

0.000195

AC:

AN:

5122

European-Non Finnish (NFE)

AF:

0.000115

AC:

102

AN:

887726

Other (OTH)

AF:

0.0000595

AC:

AN:

50396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000212

AC:

AN:

146176

Hom.:

Cov.:

AF XY:

0.000224

AC XY:

AN XY:

71304

show subpopulations

African (AFR)

AF:

0.0000257

AC:

AN:

38950

American (AMR)

AF:

0.000749

AC:

AN:

14678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3336

East Asian (EAS)

AF:

0.00

AC:

AN:

5046

South Asian (SAS)

AF:

0.000437

AC:

AN:

4576

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000256

AC:

AN:

66350

Other (OTH)

AF:

0.00

AC:

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over