Genetic Variant RMDN2:p.Ile115Lys (chr2-37929621-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001170791.3(RMDN2):c.344T>A(p.Ile115Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 1,551,354 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

RMDN2
NM_001170791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.304

Publications

1 publications found

Variant links:

Genes affected

RMDN2 (HGNC:26567): (regulator of microtubule dynamics 2) Enables microtubule binding activity. Located in Golgi apparatus; cytosol; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

RMDN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004174918).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170791.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RMDN2	NM_001170791.3	MANE Select	c.344T>A	p.Ile115Lys	missense	Exon 2 of 11	NP_001164262.1	Q96LZ7-1
RMDN2	NM_001170792.3		c.344T>A	p.Ile115Lys	missense	Exon 2 of 11	NP_001164263.1	Q96LZ7-1
RMDN2	NM_001322211.2		c.344T>A	p.Ile115Lys	missense	Exon 2 of 11	NP_001309140.1	Q96LZ7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RMDN2	ENST00000354545.8	TSL:1 MANE Select	c.344T>A	p.Ile115Lys	missense	Exon 2 of 11	ENSP00000346549.3	Q96LZ7-1
RMDN2	ENST00000406384.5	TSL:1	c.344T>A	p.Ile115Lys	missense	Exon 2 of 11	ENSP00000386004.1	Q96LZ7-1
RMDN2	ENST00000894801.1		c.344T>A	p.Ile115Lys	missense	Exon 2 of 11	ENSP00000564860.1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00108

AC:

167

AN:

154498

AF XY:

0.000854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000682

GnomAD4 exome

AF:

0.000150

AC:

210

AN:

1399302

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

690150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31594

American (AMR)

AF:

0.00580

AC:

207

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35718

South Asian (SAS)

AF:

0.00

AC:

AN:

79216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078872

Other (OTH)

AF:

0.0000517

AC:

AN:

58032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.000197

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41364

American (AMR)

AF:

0.00196

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

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:

0.000158

Hom.:

Bravo

AF:

0.000404

ExAC

AF:

0.0000401

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

7.6

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0070

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.53

M_CAP

Benign

0.0091

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

0.30

PROVEAN

Benign

-1.5

REVEL

Benign

0.11

Sift

Benign

0.59

Sift4G

Benign

0.93

Polyphen

0.095

Vest4

0.18

MVP

0.14

ClinPred

0.022

GERP RS

0.49

Varity_R

0.095

Mutation Taster

=100/0

polymorphism

(source)

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over