Variant 2-37929609-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001170791.3(RMDN2):c.332T>G(p.Leu111Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000748 in 1,551,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

RMDN2
NM_001170791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.42

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35251552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMDN2	NM_001170791.3 linkuse as main transcript	c.332T>G	p.Leu111Arg	missense_variant	2/11	ENST00000354545.8	NP_001164262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMDN2	ENST00000354545.8 linkuse as main transcript	c.332T>G	p.Leu111Arg	missense_variant	2/11	1	NM_001170791.3	ENSP00000346549	P1	Q96LZ7-1
RMDN2	ENST00000406384.5 linkuse as main transcript	c.332T>G	p.Leu111Arg	missense_variant	2/11	1		ENSP00000386004	P1	Q96LZ7-1
RMDN2	ENST00000414644.5 linkuse as main transcript	c.332T>G	p.Leu111Arg	missense_variant	2/3	5		ENSP00000393705
RMDN2	ENST00000440353.5 linkuse as main transcript	c.332T>G	p.Leu111Arg	missense_variant, NMD_transcript_variant	2/9	2		ENSP00000399495

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000323

AC:

AN:

154770

Hom.:

AF XY:

0.0000244

AC XY:

AN XY:

82038

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000853

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000715

AC:

100

AN:

1399316

Hom.:

Cov.:

AF XY:

0.0000724

AC XY:

AN XY:

690132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000908

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

AF:

0.000105

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.332T>G (p.L111R) alteration is located in exon 2 (coding exon 1) of the RMDN2 gene. This alteration results from a T to G substitution at nucleotide position 332, causing the leucine (L) at amino acid position 111 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

.;T;T

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.71

T;.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.3

.;M;M

MutationTaster

Benign

1.0

D;D

PROVEAN

Uncertain

-3.0

D;N;N

REVEL

Benign

0.24

Sift

Benign

0.084

T;D;D

Sift4G

Benign

0.17

T;T;T

Polyphen

0.71

.;P;P

Vest4

0.50, 0.41

MutPred

0.53

Gain of sheet (P = 0.0036);Gain of sheet (P = 0.0036);Gain of sheet (P = 0.0036);

MVP

0.44

ClinPred

0.32

GERP RS

6.0

Varity_R

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over