2-37951361-C-A

Variant names:

• chr2-37951361-C-A
• rs1187495842
• NM_001170791.3:c.452+21632C>A

Variant summary

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

The NM_144713.5(RMDN2):​c.146C>A​(p.Ser49Tyr) variant causes a missense 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S49F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RMDN2 NM_144713.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• 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=0.10489866).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144713.5. 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+21632C>A		intron	N/A	NP_001164262.1	Q96LZ7-1
	RMDN2	NM_144713.5		c.146C>A	p.Ser49Tyr	missense	Exon 2 of 11	NP_653314.3	A0A0C4DFM4
	RMDN2	NM_001170792.3		c.452+21632C>A		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+21632C>A		intron	N/A	ENSP00000346549.3	Q96LZ7-1
	RMDN2	ENST00000406384.5	TSL:1	c.452+21632C>A		intron	N/A	ENSP00000386004.1	Q96LZ7-1
	RMDN2	ENST00000417700.6	TSL:1	c.17+766C>A		intron	N/A	ENSP00000392977.2	Q96LZ7-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.2
DANN	Uncertain	0.98
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.12
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.073
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.10	T
Vest4		0.19
MutPred		0.24		Gain of sheet (P = 0.0266)
MVP		0.25
MPC		0.012
ClinPred		0.49	T
GERP RS		0.21
gMVP		0.036
Mutation Taster		=98/2	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: rs1187495842; hg19: chr2-38178504;