8-26657942-T-C

Variant names:

• chr8-26657942-T-C
• rs17666
• NM_001197293.3:c.*2236T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001197293.3(DPYSL2):​c.*2236T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,472 control chromosomes in the GnomAD database, including 9,736 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 0.34 (9723 hom., cov: 32)
  • Exomes 𝑓: 0.25 (13 hom.)
• Consequence: DPYSL2 NM_001197293.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323
• Publications: 15 publications found

Genes affected

DPYSL2 (HGNC:3014): (dihydropyrimidinase like 2) This gene encodes a member of the collapsin response mediator protein family. Collapsin response mediator proteins form homo- and hetero-tetramers and facilitate neuron guidance, growth and polarity. The encoded protein promotes microtubule assembly and is required for Sema3A-mediated growth cone collapse, and also plays a role in synaptic signaling through interactions with calcium channels. This gene has been implicated in multiple neurological disorders, and hyperphosphorylation of the encoded protein may play a key role in the development of Alzheimer's disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

DPYSL2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197293.3. 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
	DPYSL2	NM_001197293.3	MANE Select	c.*2236T>C		3_prime_UTR	Exon 14 of 14	NP_001184222.1
	DPYSL2	NM_001386.6		c.*2236T>C		3_prime_UTR	Exon 14 of 14	NP_001377.1
	DPYSL2	NM_001244604.2		c.*2236T>C		3_prime_UTR	Exon 14 of 14	NP_001231533.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL2	ENST00000521913.7	TSL:1 MANE Select	c.*2236T>C		3_prime_UTR	Exon 14 of 14	ENSP00000427985.2
	DPYSL2	ENST00000311151.9	TSL:1	c.*2236T>C		3_prime_UTR	Exon 14 of 14	ENSP00000309539.5

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52171 AN: 151922 Hom.: 9702 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.255 AC: 110 AN: 432 Hom.: 13 Cov.: 0 AF XY: 0.273 AC XY: 71 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.256 AC: 109 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.344 AC: 52245 AN: 152040 Hom.: 9723 Cov.: 32 AF XY: 0.343 AC XY: 25471 AN XY: 74358

African (AFR) AF: 0.467 AC: 19337 AN: 41420

American (AMR) AF: 0.259 AC: 3954 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3466

East Asian (EAS) AF: 0.121 AC: 627 AN: 5184

South Asian (SAS) AF: 0.462 AC: 2225 AN: 4818

European-Finnish (FIN) AF: 0.269 AC: 2849 AN: 10582

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21100 AN: 67978

Other (OTH) AF: 0.364 AC: 767 AN: 2110

Alfa AF: 0.325 Hom.: 15570

Bravo AF: 0.341

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	10
DANN	Benign	0.87
PhyloP100		0.32
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: rs17666; hg19: chr8-26515458; COSMIC: COSV60783800; COSMIC: COSV60783800;