2-38001525-A-G

Variant names:

• chr2-38001525-A-G
• rs1374196
• NM_001170791.3:c.1045-2466A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001170791.3(RMDN2):​c.1045-2466A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,090 control chromosomes in the GnomAD database, including 18,958 homozygotes. 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: 𝑓 0.46 (18958 hom., cov: 32)
• Consequence: RMDN2 NM_001170791.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

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.1045-2466A>G		intron	N/A	NP_001164262.1	Q96LZ7-1
	RMDN2	NM_144713.5		c.1579-2466A>G		intron	N/A	NP_653314.3	A0A0C4DFM4
	RMDN2	NM_001170792.3		c.1045-2466A>G		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.1045-2466A>G		intron	N/A	ENSP00000346549.3	Q96LZ7-1
	RMDN2	ENST00000406384.5	TSL:1	c.1045-2466A>G		intron	N/A	ENSP00000386004.1	Q96LZ7-1
	RMDN2	ENST00000417700.6	TSL:1	c.610-2466A>G		intron	N/A	ENSP00000392977.2	Q96LZ7-4

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70293 AN: 151970 Hom.: 18928 Cov.: 32

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.463 AC: 70383 AN: 152090 Hom.: 18958 Cov.: 32 AF XY: 0.466 AC XY: 34659 AN XY: 74346

African (AFR) AF: 0.719 AC: 29821 AN: 41478

American (AMR) AF: 0.513 AC: 7848 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1678 AN: 3472

East Asian (EAS) AF: 0.778 AC: 4033 AN: 5186

South Asian (SAS) AF: 0.357 AC: 1722 AN: 4820

European-Finnish (FIN) AF: 0.333 AC: 3519 AN: 10568

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20442 AN: 67968

Other (OTH) AF: 0.449 AC: 949 AN: 2112

Alfa AF: 0.382 Hom.: 3080

Bravo AF: 0.495

Asia WGS AF: 0.583 AC: 2025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.9
DANN	Benign	0.83
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs1374196; hg19: chr2-38228668;