NM_001170791.3:c.452+21574C>A

Variant names:

• chr2-37951303-C-A
• rs141147110
• NM_001170791.3:c.452+21574C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001170791.3(RMDN2):​c.452+21574C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RMDN2 NM_001170791.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06442088).

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+21574C>A		intron	N/A	NP_001164262.1	Q96LZ7-1
	RMDN2	NM_144713.5		c.88C>A	p.Arg30Ser	missense	Exon 2 of 11	NP_653314.3	A0A0C4DFM4
	RMDN2	NM_001170792.3		c.452+21574C>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+21574C>A		intron	N/A	ENSP00000346549.3	Q96LZ7-1
	RMDN2	ENST00000406384.5	TSL:1	c.452+21574C>A		intron	N/A	ENSP00000386004.1	Q96LZ7-1
	RMDN2	ENST00000417700.6	TSL:1	c.17+708C>A		intron	N/A	ENSP00000392977.2	Q96LZ7-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460274 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726502

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111412

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.5
DANN	Benign	0.93
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.63
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.063
Sift	Benign	0.048	D
Sift4G	Benign	0.16	T
Vest4		0.16
MutPred		0.16		Gain of glycosylation at R30 (P = 0.0036)
MVP		0.13
MPC		0.0049
ClinPred		0.29	T
GERP RS		2.3
gMVP		0.056
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs141147110; hg19: chr2-38178446;