2-37951541-A-G

Variant summary

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

The ENST00000354545.8(RMDN2):​c.452+21812A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000738 in 1,612,374 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: 32)
Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

RMDN2
ENST00000354545.8 intron

Scores

3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.261
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-AS1 (HGNC:41150): (RMDN2 antisense RNA 1)

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=0.06858984).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RMDN2NM_001170791.3 linkuse as main transcriptc.452+21812A>G intron_variant ENST00000354545.8 NP_001164262.1
RMDN2-AS1NR_102712.1 linkuse as main transcriptn.323-1004T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RMDN2ENST00000354545.8 linkuse as main transcriptc.452+21812A>G intron_variant 1 NM_001170791.3 ENSP00000346549 P1Q96LZ7-1
RMDN2-AS1ENST00000630021.2 linkuse as main transcriptn.427-1004T>C intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152096
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000478
GnomAD3 exomes
AF:
0.000104
AC:
26
AN:
249294
Hom.:
0
AF XY:
0.000126
AC XY:
17
AN XY:
134918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
0.000222
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000705
AC:
103
AN:
1460278
Hom.:
0
Cov.:
34
AF XY:
0.0000688
AC XY:
50
AN XY:
726484
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000672
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000792
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152096
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000478
Alfa
AF:
0.000271
Hom.:
0
Bravo
AF:
0.0000907
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000115
AC:
14
EpiCase
AF:
0.000109
EpiControl
AF:
0.000356

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 submitterclinical testingAmbry GeneticsJun 16, 2023The c.326A>G (p.D109G) alteration is located in exon 2 (coding exon 2) of the RMDN2 gene. This alteration results from a A to G substitution at nucleotide position 326, causing the aspartic acid (D) at amino acid position 109 to be replaced by a glycine (G). 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
-0.42
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
5.2
DANN
Uncertain
0.99
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.57
T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.069
T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.73
N;N;D
REVEL
Benign
0.041
Sift
Uncertain
0.0050
D;D;D
Sift4G
Uncertain
0.057
T;T;T
Vest4
0.32
MVP
0.099
MPC
0.010
ClinPred
0.10
T
GERP RS
1.4
gMVP
0.025

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.

Other links and lift over

dbSNP: rs370260752; hg19: chr2-38178684; API