chr17-63713850-T-G

Position:

• chr17-63713850-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
STRADA	NM_001003787.4	c.226+156A>C		intron_variant		ENST00000336174.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRADA	ENST00000336174.12	c.226+156A>C		intron_variant		1	NM_001003787.4	P1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106196 AN: 151864 Hom.: 38558 Cov.: 30

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.: 30 AF XY: 0.700 AC XY: 52000 AN XY: 74274

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.657

Alfa AF: 0.605 Hom.: 6797

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
DANN	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs1043127; hg19: chr17-61791210;