Genetic Variant RASD2:p.Thr11Lys (chr22-35546841-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_014310.4(RASD2):c.32C>A(p.Thr11Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T11M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RASD2
NM_014310.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.99

Publications

0 publications found

Variant links:

Genes affected

RASD2 (HGNC:18229): (RASD family member 2) This gene belongs to the Ras superfamily of small GTPases and is enriched in the striatum. The encoded protein functions as an E3 ligase for attachment of small ubiquitin-like modifier (SUMO). This protein also binds to mutant huntingtin (mHtt), the protein mutated in Huntington disease (HD). Sumoylation of mHTT by this protein may cause degeneration of the striatum. The protein functions as an activator of mechanistic target of rapamycin 1 (mTOR1), which in turn plays a role in myelination, axon growth and regeneration. Reduced levels of mRNA expressed by this gene were found in HD patients. [provided by RefSeq, Jan 2016]

RASD2 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=0.14361471).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014310.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RASD2	NM_014310.4	MANE Select	c.32C>A	p.Thr11Lys	missense	Exon 2 of 3	NP_055125.2
RASD2	NM_001366725.1		c.32C>A	p.Thr11Lys	missense	Exon 2 of 3	NP_001353654.1	Q96D21
RASD2	NM_001376515.1		c.32C>A	p.Thr11Lys	missense	Exon 2 of 3	NP_001363444.1	Q96D21

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RASD2	ENST00000216127.5	TSL:1 MANE Select	c.32C>A	p.Thr11Lys	missense	Exon 2 of 3	ENSP00000216127.4	Q96D21
RASD2	ENST00000885869.1		c.32C>A	p.Thr11Lys	missense	Exon 2 of 3	ENSP00000555928.1
RASD2	ENST00000885870.1		c.32C>A	p.Thr11Lys	missense	Exon 2 of 3	ENSP00000555929.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461658

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111906

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.11

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.018

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.75

M_CAP

Benign

0.012

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.69

PhyloP100

4.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.71

REVEL

Benign

0.053

Sift

Benign

0.14

Sift4G

Benign

0.75

Polyphen

0.0010

Vest4

0.30

MutPred

0.32

Gain of methylation at T11 (P = 0.0046)

MVP

0.32

MPC

0.98

ClinPred

0.57

GERP RS

5.3

Varity_R

0.16

gMVP

0.55

Mutation Taster

=69/31

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over