Genetic Variant RMDN2:c.452+21541C>A (chr2-37951270-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144713.5(RMDN2):c.55C>A(p.Pro19Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P19A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RMDN2
NM_144713.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67

Publications

0 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:

RMDN2-AS1 (HGNC:41150): (RMDN2 antisense RNA 1)

RMDN2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09297949).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144713.5. 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.452+21541C>A		intron	N/A	NP_001164262.1	Q96LZ7-1
RMDN2	NM_144713.5		c.55C>A	p.Pro19Thr	missense	Exon 2 of 11	NP_653314.3	A0A0C4DFM4
RMDN2	NM_001170792.3		c.452+21541C>A		intron	N/A	NP_001164263.1	Q96LZ7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RMDN2	ENST00000354545.8	TSL:1 MANE Select	c.452+21541C>A	intron	N/A	ENSP00000346549.3	Q96LZ7-1
RMDN2	ENST00000406384.5	TSL:1	c.452+21541C>A	intron	N/A	ENSP00000386004.1	Q96LZ7-1
RMDN2	ENST00000417700.6	TSL:1	c.17+675C>A	intron	N/A	ENSP00000392977.2	Q96LZ7-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452332

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722704

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32774

American (AMR)

AF:

0.00

AC:

AN:

42122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25476

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

85210

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109292

Other (OTH)

AF:

0.00

AC:

AN:

59924

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.39

(source)

DANN

Benign

0.78

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.51

M_CAP

Benign

0.0046

MetaRNN

Benign

0.093

MetaSVM

Benign

-1.0

PhyloP100

-1.7

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.86

REVEL

Benign

0.061

Sift

Benign

0.068

Sift4G

Pathogenic

0.0

Vest4

0.11

MutPred

0.098

Gain of phosphorylation at P19 (P = 0.0554)

MVP

0.067

MPC

0.0074

ClinPred

0.044

GERP RS

-5.7

gMVP

0.093

Mutation Taster

=93/7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over