Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001003787.4(STRADA):c.508C>G(p.Leu170Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 1,614,006 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L170L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 4 hom. )

Consequence

STRADA
NM_001003787.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.04

Publications

1 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: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008486122).

BP6

Variant 17-63710564-G-C is Benign according to our data. Variant chr17-63710564-G-C is described in ClinVar as Benign. ClinVar VariationId is 468884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0036 (549/152306) while in subpopulation AFR AF = 0.0124 (514/41558). AF 95% confidence interval is 0.0115. There are 3 homozygotes in GnomAd4. There are 270 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

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
STRADA	NM_001003787.4	MANE Select	c.508C>G	p.Leu170Val	missense	Exon 8 of 13	NP_001003787.1
STRADA	NM_001363786.1		c.484C>G	p.Leu162Val	missense	Exon 8 of 13	NP_001350715.1
STRADA	NM_001363787.1		c.421C>G	p.Leu141Val	missense	Exon 6 of 11	NP_001350716.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STRADA	ENST00000336174.12	TSL:1 MANE Select	c.508C>G	p.Leu170Val	missense	Exon 8 of 13	ENSP00000336655.6
STRADA	ENST00000375840.9	TSL:1	c.334C>G	p.Leu112Val	missense	Exon 7 of 12	ENSP00000365000.4
STRADA	ENST00000392950.9	TSL:1	c.397C>G	p.Leu133Val	missense	Exon 6 of 9	ENSP00000376677.4

Frequencies

GnomAD3 genomes

AF:

0.00358

AC:

545

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

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:

0.0000294

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00118

AC:

296

AN:

251224

AF XY:

0.000891

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000391

AC:

571

AN:

1461700

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

235

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.0128

AC:

427

AN:

33472

American (AMR)

AF:

0.00148

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1111874

Other (OTH)

AF:

0.00106

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00360

AC:

549

AN:

152306

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

270

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0124

AC:

514

AN:

41558

American (AMR)

AF:

0.00177

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

101

135

169

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:

0.000635

Hom.:

Bravo

AF:

0.00443

ESP6500AA

AF:

0.0134

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00135

AC:

164

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Polyhydramnios, megalencephaly, and symptomatic epilepsy (1)

STRADA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.057

Eigen

Benign

-0.011

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0085

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.41

PhyloP100

3.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.33

REVEL

Benign

0.084

Sift

Benign

0.48

Sift4G

Benign

0.56

Polyphen

0.95

Vest4

0.57

MVP

0.76

MPC

0.93

ClinPred

0.0098

GERP RS

4.6

Varity_R

0.22

gMVP

0.56

Mutation Taster

=96/4

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.

rs61734984

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over