NM_001170791.3:c.452+21821C>T

Variant names:

• chr2-37951550-C-T
• NM_001170791.3:c.452+21821C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170791.3(RMDN2):​c.452+21821C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RMDN2 NM_001170791.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.509
• 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09218922).

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.452+21821C>T		intron	N/A	NP_001164262.1	Q96LZ7-1
	RMDN2	NM_144713.5		c.335C>T	p.Ser112Phe	missense	Exon 2 of 11	NP_653314.3	A0A0C4DFM4
	RMDN2	NM_001170792.3		c.452+21821C>T		intron	N/A	NP_001164263.1	Q96LZ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMDN2	ENST00000354545.8	TSL:1 MANE Select	c.452+21821C>T		intron	N/A	ENSP00000346549.3	Q96LZ7-1
	RMDN2	ENST00000406384.5	TSL:1	c.452+21821C>T		intron	N/A	ENSP00000386004.1	Q96LZ7-1
	RMDN2	ENST00000417700.6	TSL:1	c.17+955C>T		intron	N/A	ENSP00000392977.2	Q96LZ7-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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	0.17
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Uncertain	1.0
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.51
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.082
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Vest4		0.30
MutPred		0.24		Gain of sheet (P = 0.0149)
MVP		0.18
MPC		0.021
ClinPred		0.98	D
GERP RS		1.7
gMVP		0.022
Mutation Taster		=97/3	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

hg19: chr2-38178693;