rs1062715

Variant names:

• chr1-205160191-G-A
• rs1062715
• NM_015375.3:c.2028C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-205160191-G-A
• chr1-205160191-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_015375.3(DSTYK):​c.2028C>T​(p.Phe676Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,613,754 control chromosomes in the GnomAD database, including 59,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7249 hom., cov: 32)
  • Exomes 𝑓: 0.26 (52282 hom.)
• Consequence: DSTYK NM_015375.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.66
• Publications: 17 publications found

Genes affected

DSTYK (HGNC:29043): (dual serine/threonine and tyrosine protein kinase) This gene encodes a dual serine/threonine and tyrosine protein kinase which is expressed in multiple tissues. It is thought to function as a regulator of cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

DSTYK Gene-Disease associations (from GenCC):

• congenital anomalies of kidney and urinary tract 1

  Inheritance: AD, AR Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• hereditary spastic paraplegia 23

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet
• complex hereditary spastic paraplegia

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• renal agenesis, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 1-205160191-G-A is Benign according to our data. Variant chr1-205160191-G-A is described in ClinVar as Benign. ClinVar VariationId is 260658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.66 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015375.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSTYK	NM_015375.3	MANE Select	c.2028C>T	p.Phe676Phe	synonymous	Exon 8 of 13	NP_056190.1
	DSTYK	NM_199462.3		c.2028C>T	p.Phe676Phe	synonymous	Exon 8 of 12	NP_955749.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSTYK	ENST00000367162.8	TSL:1 MANE Select	c.2028C>T	p.Phe676Phe	synonymous	Exon 8 of 13	ENSP00000356130.3
	DSTYK	ENST00000367161.7	TSL:1	c.2028C>T	p.Phe676Phe	synonymous	Exon 8 of 12	ENSP00000356129.3
	DSTYK	ENST00000893236.1		c.2001C>T	p.Phe667Phe	synonymous	Exon 8 of 13	ENSP00000563295.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45484 AN: 151854 Hom.: 7241 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.300

GnomAD2 exomes AF: 0.303 AC: 76058 AN: 251378 AF XY: 0.301

Gnomad AFR exome AF: 0.385

Gnomad AMR exome AF: 0.339

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.415

Gnomad FIN exome AF: 0.314

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.261 AC: 381723 AN: 1461782 Hom.: 52282 Cov.: 37 AF XY: 0.264 AC XY: 192092 AN XY: 727194

African (AFR) AF: 0.374 AC: 12530 AN: 33480

American (AMR) AF: 0.341 AC: 15258 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 7544 AN: 26134

East Asian (EAS) AF: 0.406 AC: 16132 AN: 39698

South Asian (SAS) AF: 0.406 AC: 35059 AN: 86254

European-Finnish (FIN) AF: 0.311 AC: 16601 AN: 53420

Middle Eastern (MID) AF: 0.240 AC: 1384 AN: 5762

European-Non Finnish (NFE) AF: 0.234 AC: 260469 AN: 1111924

Other (OTH) AF: 0.277 AC: 16746 AN: 60388

GnomAD4 genome AF: 0.300 AC: 45517 AN: 151972 Hom.: 7249 Cov.: 32 AF XY: 0.305 AC XY: 22670 AN XY: 74262

African (AFR) AF: 0.377 AC: 15605 AN: 41444

American (AMR) AF: 0.315 AC: 4808 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1021 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2050 AN: 5148

South Asian (SAS) AF: 0.412 AC: 1984 AN: 4814

European-Finnish (FIN) AF: 0.313 AC: 3305 AN: 10546

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15749 AN: 67966

Other (OTH) AF: 0.300 AC: 633 AN: 2108

Alfa AF: 0.262 Hom.: 4206

Bravo AF: 0.306

Asia WGS AF: 0.393 AC: 1364 AN: 3478

EpiCase AF: 0.236

EpiControl AF: 0.227

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Congenital anomalies of kidney and urinary tract 1 (1)
-	-	1	Hereditary spastic paraplegia 23 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.2
DANN	Benign	0.79
PhyloP100		2.7
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: rs1062715; hg19: chr1-205129319; COSMIC: COSV65688001;