dbSNP rs376753634: SHISA2:p.Arg57Cys (chr13-26050807-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_001007538.2(SHISA2):c.169C>T(p.Arg57Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000289 in 1,385,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R57G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SHISA2
NM_001007538.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.14

Publications

0 publications found

Variant links:

Genes affected

SHISA2 (HGNC:20366): (shisa family member 2) Predicted to be involved in negative regulation of Wnt signaling pathway and negative regulation of fibroblast growth factor receptor signaling pathway. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

SHISA2 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=0.38440874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA2	NM_001007538.2 link	c.169C>T	p.Arg57Cys	missense_variant	Exon 1 of 2	ENST00000319420.4	NP_001007539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHISA2	ENST00000319420.4 link	c.169C>T	p.Arg57Cys	missense_variant	Exon 1 of 2	1	NM_001007538.2	ENSP00000313079.3		Q6UWI4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000144

AC:

AN:

138542

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000342

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1385998

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

686018

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29240

American (AMR)

AF:

0.00

AC:

AN:

37288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24604

East Asian (EAS)

AF:

0.00

AC:

AN:

34474

South Asian (SAS)

AF:

0.00

AC:

AN:

79116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4138

European-Non Finnish (NFE)

AF:

0.00000369

AC:

AN:

1085160

Other (OTH)

AF:

0.00

AC:

AN:

57802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.613

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000182

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.9

PhyloP100

4.1

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.8

REVEL

Benign

0.17

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.32

MutPred

0.41

Gain of catalytic residue at G61 (P = 0);

MVP

0.65

MPC

0.98

ClinPred

0.95

GERP RS

4.3

Varity_R

0.31

gMVP

0.70

Mutation Taster

=63/37

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over