12-56586850-G-A

Variant names:

• chr12-56586850-G-A
• NM_002898.4:c.875G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002898.4(RBMS2):​c.875G>A​(p.Arg292Lys) variant causes a missense, splice region 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. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBMS2 NM_002898.4 missense, splice_region
• Scores: Splicing: ADA: 0.01044
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.473

Genes affected

RBMS2 (HGNC:9909): (RNA binding motif single stranded interacting protein 2) The protein encoded by this gene is a member of a small family of proteins which bind single stranded DNA/RNA. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. The RBMS proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. This protein was isolated by phenotypic complementation of cdc2 and cdc13 mutants of yeast and is thought to suppress cdc2 and cdc13 mutants through the induction of translation of cdc2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09336582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMS2	NM_002898.4	c.875G>A	p.Arg292Lys	missense_variant, splice_region_variant	Exon 10 of 14	ENST00000262031.10	NP_002889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMS2	ENST00000262031.10	c.875G>A	p.Arg292Lys	missense_variant, splice_region_variant	Exon 10 of 14	1	NM_002898.4	ENSP00000262031.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.875G>A (p.R292K) alteration is located in exon 10 (coding exon 10) of the RBMS2 gene. This alteration results from a G to A substitution at nucleotide position 875, causing the arginine (R) at amino acid position 292 to be replaced by a lysine (K). 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	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.034	T;.;.
Eigen	Benign	-0.079
Eigen_PC	Benign	0.044
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.62	T;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.093	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.24	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.99	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.0030	B;B;D
Vest4		0.19
MutPred		0.31		Gain of methylation at R292 (P = 0.0073);.;.;
MVP		0.37
MPC		0.32
ClinPred		0.49	T
GERP RS		4.0
Varity_R		0.12
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.010
dbscSNV1_RF	Benign	0.082
SpliceAI score (max)		0.010		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: chr12-56980634;