rs372229032

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS1

The NM_001003787.4(STRADA):c.922G>A(p.Glu308Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000166 in 1,597,924 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E308E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

STRADA
NM_001003787.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 4.37

Publications

2 publications found

Variant links:

Genes affected

STRADA (HGNC:30172): (STE20 related adaptor alpha) The protein encoded by this gene contains a STE20-like kinase domain, but lacks several residues that are critical for catalytic activity, so it is termed a 'pseudokinase'. The protein forms a heterotrimeric complex with serine/threonine kinase 11 (STK11, also known as LKB1) and the scaffolding protein calcium binding protein 39 (CAB39, also known as MO25). The protein activates STK11 leading to the phosphorylation of both proteins and excluding STK11 from the nucleus. The protein is necessary for STK11-induced G1 cell cycle arrest. A mutation in this gene has been shown to result in polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE) syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. Additional transcript variants have been described but their full-length nature is not known. [provided by RefSeq, Sep 2009]

STRADA Gene-Disease associations (from GenCC):

polyhydramnios, megalencephaly, and symptomatic epilepsy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia

STRADA links:

ENSG00000125695 (HGNC:):

ENSG00000125695 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13067394).

BP6

Variant 17-63704519-C-T is Benign according to our data. Variant chr17-63704519-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 468889.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000141 (21/149148) while in subpopulation NFE AF = 0.00031 (21/67696). AF 95% confidence interval is 0.000208. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003787.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STRADA	NM_001003787.4	MANE Select	c.922G>A	p.Glu308Lys	missense	Exon 11 of 13	NP_001003787.1	Q7RTN6-1
STRADA	NM_001363786.1		c.898G>A	p.Glu300Lys	missense	Exon 11 of 13	NP_001350715.1
STRADA	NM_001363787.1		c.835G>A	p.Glu279Lys	missense	Exon 9 of 11	NP_001350716.1	A0A1W2PPJ9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STRADA	ENST00000336174.12	TSL:1 MANE Select	c.922G>A	p.Glu308Lys	missense	Exon 11 of 13	ENSP00000336655.6	Q7RTN6-1
STRADA	ENST00000375840.9	TSL:1	c.748G>A	p.Glu250Lys	missense	Exon 10 of 12	ENSP00000365000.4	Q7RTN6-5
STRADA	ENST00000392950.9	TSL:1	c.811G>A	p.Glu271Lys	missense	Exon 9 of 9	ENSP00000376677.4	Q7RTN6-2

Frequencies

GnomAD3 genomes

AF:

0.000141

AC:

AN:

149148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000310

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000124

AC:

AN:

242468

AF XY:

0.000153

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:

0.0000962

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.000169

AC:

245

AN:

1448776

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

116

AN XY:

719562

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33322

American (AMR)

AF:

0.00

AC:

AN:

44168

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25208

East Asian (EAS)

AF:

0.00

AC:

AN:

39180

South Asian (SAS)

AF:

0.00

AC:

AN:

84692

European-Finnish (FIN)

AF:

0.000134

AC:

AN:

52422

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.000210

AC:

232

AN:

1104338

Other (OTH)

AF:

0.000100

AC:

AN:

59730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

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:

0.000141

AC:

AN:

149148

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

72468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40614

American (AMR)

AF:

0.00

AC:

AN:

14382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

4990

South Asian (SAS)

AF:

0.00

AC:

AN:

4728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9990

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000310

AC:

AN:

67696

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.000114

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Polyhydramnios, megalencephaly, and symptomatic epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.069

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.026

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

4.4

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.9

REVEL

Benign

0.073

Sift

Benign

0.23

Sift4G

Benign

0.52

Polyphen

0.16

Vest4

0.57

MVP

0.52

MPC

0.53

ClinPred

0.075

GERP RS

2.8

PromoterAI

-0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.41

Mutation Taster

=75/25

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over