Genetic Variant NM_002898.4:c.60C>A (chr12-56522083-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002898.4(RBMS2):c.60C>A(p.Asn20Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N20H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RBMS2
NM_002898.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.81

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:

ENSG00000298140 (HGNC:):

ENSG00000298140 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20413145).

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.60C>A	p.Asn20Lys	missense	Exon 1 of 14	NP_002889.1	Q15434
RBMS2	NM_001414460.1		c.60C>A	p.Asn20Lys	missense	Exon 1 of 13	NP_001401389.1
RBMS2	NM_001414461.1		c.60C>A	p.Asn20Lys	missense	Exon 1 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.60C>A	p.Asn20Lys	missense	Exon 1 of 14	ENSP00000262031.5	Q15434
RBMS2	ENST00000552916.5	TSL:1	n.60C>A		non_coding_transcript_exon	Exon 1 of 12	ENSP00000450127.1	F8VQS9
RBMS2	ENST00000855893.1		c.60C>A	p.Asn20Lys	missense	Exon 1 of 14	ENSP00000525952.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1443506

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719108

African (AFR)

AF:

0.00

AC:

AN:

32916

American (AMR)

AF:

0.00

AC:

AN:

44096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25984

East Asian (EAS)

AF:

0.00

AC:

AN:

39352

South Asian (SAS)

AF:

0.00

AC:

AN:

85622

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096866

Other (OTH)

AF:

0.00

AC:

AN:

59702

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.019

Eigen

Benign

-0.012

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

M_CAP

Benign

0.0042

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

3.8

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.11

REVEL

Benign

0.13

Sift

Benign

0.036

Sift4G

Benign

0.93

Polyphen

0.0

Vest4

0.46

MutPred

0.53

Gain of methylation at N20 (P = 0.0049)

MVP

0.29

MPC

0.34

ClinPred

0.62

GERP RS

5.4

PromoterAI

-0.22

Neutral

(source)

Varity_R

0.26

gMVP

0.25

Mutation Taster

=66/34

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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