rs11863

chr8-26656800-C-T

Variant summary

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

The NM_001197293.3(DPYSL2):c.*1094C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,612 control chromosomes in the GnomAD database, including 13,805 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 0.41 (13724 hom., cov: 32)
  • Exomes 𝑓: 0.54 (81 hom.)
• Consequence: DPYSL2 NM_001197293.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPYSL2	NM_001197293.3	c.*1094C>T		3_prime_UTR_variant	14/14	ENST00000521913.7
DPYSL2	NM_001244604.2	c.*1094C>T		3_prime_UTR_variant	14/14
DPYSL2	NM_001386.6	c.*1094C>T		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYSL2	ENST00000521913.7	c.*1094C>T		3_prime_UTR_variant	14/14	1	NM_001197293.3
DPYSL2	ENST00000311151.9	c.*1094C>T		3_prime_UTR_variant	14/14	1		P1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62564 AN: 151964 Hom.: 13731 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.543 AC: 288 AN: 530 Hom.: 81 Cov.: 0 AF XY: 0.518 AC XY: 173 AN XY: 334

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.560

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.411 AC: 62566 AN: 152082 Hom.: 13724 Cov.: 32 AF XY: 0.408 AC XY: 30290 AN XY: 74308

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.392

Alfa AF: 0.467 Hom.: 11108

Bravo AF: 0.391

Asia WGS AF: 0.319 AC: 1110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.012
Dann	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs11863; hg19: chr8-26514316; COSMIC: COSV60783794; COSMIC: COSV60783794;