17-63705560-C-T

Variant names:

• chr17-63705560-C-T
• rs721575
• NM_001003787.4:c.859-978G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003787.4(STRADA):​c.859-978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 155,262 control chromosomes in the GnomAD database, including 35,614 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 0.66 (35053 hom., cov: 31)
  • Exomes 𝑓: 0.57 (561 hom.)
• Consequence: STRADA NM_001003787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 31 publications found

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

ENSG00000125695 (HGNC:):

ACMG classification

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 = 0.899 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRADA	NM_001003787.4	MANE Select	c.859-978G>A		intron	N/A	NP_001003787.1	Q7RTN6-1
	STRADA	NM_001363786.1		c.835-978G>A		intron	N/A	NP_001350715.1
	STRADA	NM_001363787.1		c.772-978G>A		intron	N/A	NP_001350716.1	A0A1W2PPJ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STRADA	ENST00000336174.12	TSL:1 MANE Select	c.859-978G>A		intron	N/A	ENSP00000336655.6	Q7RTN6-1
	STRADA	ENST00000375840.9	TSL:1	c.685-978G>A		intron	N/A	ENSP00000365000.4	Q7RTN6-5
	STRADA	ENST00000392950.9	TSL:1	c.748-978G>A		intron	N/A	ENSP00000376677.4	Q7RTN6-2

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100224 AN: 151908 Hom.: 34991 Cov.: 31

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.623

GnomAD4 exome AF: 0.572 AC: 1850 AN: 3236 Hom.: 561 Cov.: 0 AF XY: 0.579 AC XY: 1011 AN XY: 1746

African (AFR) AF: 0.917 AC: 33 AN: 36

American (AMR) AF: 0.590 AC: 400 AN: 678

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 4 AN: 14

East Asian (EAS) AF: 0.583 AC: 49 AN: 84

South Asian (SAS) AF: 0.692 AC: 173 AN: 250

European-Finnish (FIN) AF: 0.563 AC: 18 AN: 32

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.545 AC: 1106 AN: 2028

Other (OTH) AF: 0.588 AC: 67 AN: 114

GnomAD4 genome AF: 0.660 AC: 100345 AN: 152026 Hom.: 35053 Cov.: 31 AF XY: 0.662 AC XY: 49148 AN XY: 74286

African (AFR) AF: 0.906 AC: 37611 AN: 41496

American (AMR) AF: 0.610 AC: 9320 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1726 AN: 3466

East Asian (EAS) AF: 0.582 AC: 3002 AN: 5156

South Asian (SAS) AF: 0.735 AC: 3543 AN: 4820

European-Finnish (FIN) AF: 0.570 AC: 6011 AN: 10542

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37234 AN: 67954

Other (OTH) AF: 0.622 AC: 1312 AN: 2110

Alfa AF: 0.583 Hom.: 50103

Bravo AF: 0.670

Asia WGS AF: 0.683 AC: 2374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.31
DANN	Benign	0.26
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs721575; hg19: chr17-61782920; COSMIC: COSV107195917; COSMIC: COSV107195917;