Variant 2-37951316-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144713.5(RMDN2):c.101C>T(p.Ser34Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,460,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

RMDN2
NM_144713.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0700

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14291286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMDN2	NM_001170791.3 link	c.452+21587C>T		intron_variant		ENST00000354545.8	NP_001164262.1	Q96LZ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMDN2	ENST00000354545.8 link	c.452+21587C>T		intron_variant		1	NM_001170791.3	ENSP00000346549.3		Q96LZ7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250438

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460734

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726664

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

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

Jul 19, 2023

The c.101C>T (p.S34F) alteration is located in exon 2 (coding exon 2) of the RMDN2 gene. This alteration results from a C to T substitution at nucleotide position 101, causing the serine (S) at amino acid position 34 to be replaced by a phenylalanine (F). 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

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.6

DANN

Uncertain

1.0

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.61

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.76

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.94

N;N;D

REVEL

Benign

0.15

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.012

D;D;T

Vest4

0.20

MutPred

0.32

Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);

MVP

0.51

MPC

0.021

ClinPred

0.63

GERP RS

4.1

gMVP

0.053

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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