Genetic Variant NM_014806.5:c.86G>A (chr9-35546607-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014806.5(RUSC2):c.86G>A(p.Cys29Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C29R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RUSC2
NM_014806.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

Publications

0 publications found

Variant links:

Genes affected

RUSC2 (HGNC:23625): (RUN and SH3 domain containing 2) This gene encodes a RUN and SH3 domain containing protein that interacts with Rab1b and Rab1-binding protein GM130. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jun 2012]

RUSC2 Gene-Disease associations (from GenCC):

intellectual disability, autosomal recessive 61
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), PanelApp Australia

RUSC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32831568).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014806.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUSC2	NM_014806.5	MANE Select	c.86G>A	p.Cys29Tyr	missense	Exon 2 of 12	NP_055621.2	Q8N2Y8
RUSC2	NM_001135999.2		c.86G>A	p.Cys29Tyr	missense	Exon 2 of 12	NP_001129471.2	Q8N2Y8
RUSC2	NM_001330740.2		c.-620-8453G>A		intron	N/A	NP_001317669.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RUSC2	ENST00000361226.8	TSL:2 MANE Select	c.86G>A	p.Cys29Tyr	missense	Exon 2 of 12	ENSP00000355177.3	Q8N2Y8
RUSC2	ENST00000455600.1	TSL:1	c.86G>A	p.Cys29Tyr	missense	Exon 2 of 12	ENSP00000393922.1	Q8N2Y8
RUSC2	ENST00000866950.1		c.86G>A	p.Cys29Tyr	missense	Exon 2 of 12	ENSP00000537009.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1399858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690920

African (AFR)

AF:

0.00

AC:

AN:

31654

American (AMR)

AF:

0.00

AC:

AN:

35080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21640

East Asian (EAS)

AF:

0.00

AC:

AN:

39000

South Asian (SAS)

AF:

0.00

AC:

AN:

74322

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5464

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083676

Other (OTH)

AF:

0.00

AC:

AN:

57696

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.045

Eigen

Benign

0.076

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

M_CAP

Benign

0.0069

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

4.1

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.1

REVEL

Benign

0.22

Sift

Benign

0.11

Sift4G

Benign

0.89

Polyphen

0.018

Vest4

0.59

MutPred

0.62

Gain of sheet (P = 0.0344)

MVP

0.41

MPC

0.65

ClinPred

0.51

GERP RS

6.1

Varity_R

0.11

gMVP

0.43

Mutation Taster

=95/5

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