2-37929569-G-C

Variant names:

• chr2-37929569-G-C
• rs1666554494
• NM_001170791.3:c.292G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001170791.3(RMDN2):​c.292G>C​(p.Glu98Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00001 in 1,399,572 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: not found (cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: RMDN2 NM_001170791.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75

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]

ACMG classification

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=0.28951684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMDN2	NM_001170791.3	c.292G>C	p.Glu98Gln	missense_variant	Exon 2 of 11	ENST00000354545.8	NP_001164262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RMDN2	ENST00000354545.8	c.292G>C	p.Glu98Gln	missense_variant	Exon 2 of 11	1	NM_001170791.3	ENSP00000346549.3
RMDN2	ENST00000406384.5	c.292G>C	p.Glu98Gln	missense_variant	Exon 2 of 11	1		ENSP00000386004.1
RMDN2	ENST00000414644.5	c.292G>C	p.Glu98Gln	missense_variant	Exon 2 of 3	5		ENSP00000393705.1
RMDN2	ENST00000440353.5	n.292G>C		non_coding_transcript_exon_variant	Exon 2 of 9	2		ENSP00000399495.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000100 AC: 14 AN: 1399572 Hom.: 0 Cov.: 31 AF XY: 0.0000130 AC XY: 9 AN XY: 690252

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: 0.0000120

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.292G>C (p.E98Q) alteration is located in exon 2 (coding exon 1) of the RMDN2 gene. This alteration results from a G to C substitution at nucleotide position 292, causing the glutamic acid (E) at amino acid position 98 to be replaced by a glutamine (Q). 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	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	.;T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D;.;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.5	.;M;M
PROVEAN	Benign	-0.90	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.047	D;T;T
Sift4G	Benign	0.10	T;T;T
Polyphen		1.0	.;D;D
Vest4		0.20, 0.20
MutPred		0.21		Loss of ubiquitination at K97 (P = 0.0429);Loss of ubiquitination at K97 (P = 0.0429);Loss of ubiquitination at K97 (P = 0.0429);
MVP		0.40
ClinPred		0.85	D
GERP RS		6.1
Varity_R		0.13

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

Other links and lift over

dbSNP: rs1666554494; hg19: chr2-38156712;