Variant 2-37929600-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001170791.3(RMDN2):c.323A>G(p.Gln108Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RMDN2
NM_001170791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.84

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046661913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMDN2	NM_001170791.3 linkuse as main transcript	c.323A>G	p.Gln108Arg	missense_variant	2/11	ENST00000354545.8	NP_001164262.1	Q96LZ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RMDN2	ENST00000354545.8 linkuse as main transcript	c.323A>G	p.Gln108Arg	missense_variant	2/11	1	NM_001170791.3	ENSP00000346549.3	Q96LZ7-1
RMDN2	ENST00000406384.5 linkuse as main transcript	c.323A>G	p.Gln108Arg	missense_variant	2/11	1		ENSP00000386004.1	Q96LZ7-1
RMDN2	ENST00000414644.5 linkuse as main transcript	c.323A>G	p.Gln108Arg	missense_variant	2/3	5		ENSP00000393705.1	C9JUD5
RMDN2	ENST00000440353.5 linkuse as main transcript	n.323A>G		non_coding_transcript_exon_variant	2/9	2		ENSP00000399495.1	F8WFC3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1399366

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

690174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000840

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Dec 03, 2024

The c.323A>G (p.Q108R) alteration is located in exon 2 (coding exon 1) of the RMDN2 gene. This alteration results from a A to G substitution at nucleotide position 323, causing the glutamine (Q) at amino acid position 108 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

0.061

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.00064

.;T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.70

T;.;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.047

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.52

.;N;N

PROVEAN

Benign

0.58

N;N;N

REVEL

Benign

0.037

Sift

Benign

0.96

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

.;B;B

Vest4

0.035, 0.029

MutPred

0.31

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);

MVP

0.19

ClinPred

0.24

GERP RS

2.5

Varity_R

0.063

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