Genetic Variant STRADA:c.226+156A>C (chr17-63713850-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001003787.4(STRADA):c.226+156A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 151,982 control chromosomes in the GnomAD database, including 38,618 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.70 ( 38618 hom., cov: 30)

Consequence

STRADA
NM_001003787.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.991

Publications

11 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRADA	NM_001003787.4 link	c.226+156A>C		intron_variant	Intron 5 of 12	ENST00000336174.12	NP_001003787.1	Q7RTN6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRADA	ENST00000336174.12 link	c.226+156A>C		intron_variant	Intron 5 of 12	1	NM_001003787.4	ENSP00000336655.6		Q7RTN6-1
ENSG00000125695	ENST00000580553.1 link	n.*264+156A>C		intron_variant	Intron 5 of 11	5		ENSP00000464100.1		J3QR89

Frequencies

GnomAD3 genomes

AF:

0.699

AC:

106196

AN:

151864

Hom.:

38558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.916

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.635

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.583

Gnomad SAS

AF:

0.746

Gnomad FIN

AF:

0.645

Gnomad MID

AF:

0.637

Gnomad NFE

AF:

0.608

Gnomad OTH

AF:

0.658

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.700

AC:

106313

AN:

151982

Hom.:

38618

Cov.:

AF XY:

0.700

AC XY:

52000

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.916

AC:

38019

AN:

41494

American (AMR)

AF:

0.635

AC:

9692

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

1886

AN:

3468

East Asian (EAS)

AF:

0.584

AC:

3018

AN:

5170

South Asian (SAS)

AF:

0.744

AC:

3588

AN:

4820

European-Finnish (FIN)

AF:

0.645

AC:

6796

AN:

10532

Middle Eastern (MID)

AF:

0.658

AC:

192

AN:

292

European-Non Finnish (NFE)

AF:

0.608

AC:

41297

AN:

67928

Other (OTH)

AF:

0.657

AC:

1387

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1493

2985

4478

5970

7463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.618

Hom.:

9299

Bravo

AF:

0.704

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.4

(source)

DANN

Benign

0.65

PhyloP100

-0.99

PromoterAI

0.0078

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over