chr2-37929388-G-A

Position:

• chr2-37929388-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001170791.3(RMDN2):​c.111G>A​(p.Met37Ile) 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RMDN2 NM_001170791.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06622377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RMDN2	NM_001170791.3	c.111G>A	p.Met37Ile	missense_variant	2/11	ENST00000354545.8	NP_001164262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMDN2	ENST00000354545.8	c.111G>A	p.Met37Ile	missense_variant	2/11	1	NM_001170791.3	ENSP00000346549	P1
RMDN2	ENST00000406384.5	c.111G>A	p.Met37Ile	missense_variant	2/11	1		ENSP00000386004	P1
RMDN2	ENST00000414644.5	c.111G>A	p.Met37Ile	missense_variant	2/3	5		ENSP00000393705
RMDN2	ENST00000440353.5	c.111G>A	p.Met37Ile	missense_variant, NMD_transcript_variant	2/9	2		ENSP00000399495

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2023

The c.111G>A (p.M37I) alteration is located in exon 2 (coding exon 1) of the RMDN2 gene. This alteration results from a G to A substitution at nucleotide position 111, causing the methionine (M) at amino acid position 37 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.59
DEOGEN2	Benign	0.0041	.;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.65	T;.;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.066	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	.;M;M
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.023
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.66	T;T;T
Polyphen		0.0070	.;B;B
Vest4		0.14, 0.12
MutPred		0.28		Gain of methylation at K38 (P = 0.0343);Gain of methylation at K38 (P = 0.0343);Gain of methylation at K38 (P = 0.0343);
MVP		0.17
ClinPred		0.067	T
GERP RS		3.5
Varity_R		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-38156531;