chr2-37929569-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28951684).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170791.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMDN2	NM_001170791.3	MANE Select	c.292G>C	p.Glu98Gln	missense	Exon 2 of 11	NP_001164262.1	Q96LZ7-1
	RMDN2	NM_001170792.3		c.292G>C	p.Glu98Gln	missense	Exon 2 of 11	NP_001164263.1	Q96LZ7-1
	RMDN2	NM_001322211.2		c.292G>C	p.Glu98Gln	missense	Exon 2 of 11	NP_001309140.1	Q96LZ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMDN2	ENST00000354545.8	TSL:1 MANE Select	c.292G>C	p.Glu98Gln	missense	Exon 2 of 11	ENSP00000346549.3	Q96LZ7-1
	RMDN2	ENST00000406384.5	TSL:1	c.292G>C	p.Glu98Gln	missense	Exon 2 of 11	ENSP00000386004.1	Q96LZ7-1
	RMDN2	ENST00000894801.1		c.292G>C	p.Glu98Gln	missense	Exon 2 of 11	ENSP00000564860.1

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

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35720

South Asian (SAS) AF: 0.00 AC: 0 AN: 79220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.0000120 AC: 13 AN: 1078978

Other (OTH) AF: 0.0000172 AC: 1 AN: 58070

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.7
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.15
Sift	Benign	0.047	D
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.21		Loss of ubiquitination at K97 (P = 0.0429)
MVP		0.40
ClinPred		0.85	D
GERP RS		6.1
Varity_R		0.13
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1666554494; hg19: chr2-38156712;