Genetic Variant NM_002898.4:c.236A>G (chr12-56568977-A-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002898.4(RBMS2):c.236A>G(p.Tyr79Cys) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

RBMS2
NM_002898.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.82

Publications

0 publications found

Variant links:

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]

RBMS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.868

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBMS2	NM_002898.4	MANE Select	c.236A>G	p.Tyr79Cys	missense splice_region	Exon 3 of 14	NP_002889.1	Q15434
RBMS2	NM_001414460.1		c.236A>G	p.Tyr79Cys	missense splice_region	Exon 3 of 13	NP_001401389.1
RBMS2	NM_001414461.1		c.236A>G	p.Tyr79Cys	missense splice_region	Exon 3 of 14	NP_001401390.1	Q15434

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBMS2	ENST00000262031.10	TSL:1 MANE Select	c.236A>G	p.Tyr79Cys	missense splice_region	Exon 3 of 14	ENSP00000262031.5	Q15434
RBMS2	ENST00000552916.5	TSL:1	n.234-922A>G		intron	N/A	ENSP00000450127.1	F8VQS9
RBMS2	ENST00000550726.5	TSL:2	c.-140A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 13	ENSP00000449678.1	F8VV01

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.043

MetaRNN

Pathogenic

0.87

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.87

PhyloP100

8.8

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-7.9

REVEL

Pathogenic

0.69

Sift

Uncertain

0.015

Sift4G

Uncertain

0.031

Polyphen

0.97

Vest4

0.82

MutPred

0.73

Gain of catalytic residue at P78 (P = 0.0087)

MVP

0.78

MPC

1.1

ClinPred

1.0

GERP RS

5.2

Varity_R

0.74

gMVP

0.66

Mutation Taster

=17/83

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over