Genetic Variant SHISA2:p.Arg57Gly (chr13-26050807-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001007538.2(SHISA2):c.169C>G(p.Arg57Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000131 in 1,538,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SHISA2
NM_001007538.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14707747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA2	NM_001007538.2 link	c.169C>G	p.Arg57Gly	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>G	p.Arg57Gly	missense_variant	Exon 1 of 2	1	NM_001007538.2	ENSP00000313079.3		Q6UWI4

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000505

AC:

AN:

138542

AF XY:

0.0000257

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:

0.000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

191

AN:

1386000

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

686018

show subpopulations

African (AFR)

AF:

0.0000342

AC:

AN:

29242

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:

0.0000126

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:

0.000162

AC:

176

AN:

1085160

Other (OTH)

AF:

0.000225

AC:

AN:

57802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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

AF:

0.0000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000425

AC:

ExAC

AF:

0.0000365

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 15, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.169C>G (p.R57G) alteration is located in exon 1 (coding exon 1) of the SHISA2 gene. This alteration results from a C to G substitution at nucleotide position 169, causing the arginine (R) at amino acid position 57 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.47

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.086

Eigen

Benign

-0.11

Eigen_PC

Benign

0.035

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

4.1

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.4

REVEL

Benign

0.036

Sift

Benign

0.046

Sift4G

Benign

0.081

Polyphen

0.0030

Vest4

0.27

MVP

0.42

MPC

0.75

ClinPred

0.19

GERP RS

4.3

Varity_R

0.30

gMVP

0.70

Mutation Taster

=54/46

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over