8-26577755-C-T

Position:

• chr8-26577755-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.355-4214C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 964,490 control chromosomes in the GnomAD database, including 290,097 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 0.71 (40046 hom., cov: 35)
  • Exomes 𝑓: 0.78 (250051 hom.)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441

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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.355-4214C>T		intron_variant		ENST00000521913.7	NP_001184222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.355-4214C>T		intron_variant		1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000493789.6	c.255+388C>T		intron_variant		4		ENSP00000427954.1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108322 AN: 151766 Hom.: 40041 Cov.: 35

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.716

GnomAD4 exome AF: 0.783 AC: 636124 AN: 812616 Hom.: 250051 AF XY: 0.783 AC XY: 294494 AN XY: 375896

Gnomad4 AFR exome AF: 0.462

Gnomad4 AMR exome AF: 0.834

Gnomad4 ASJ exome AF: 0.774

Gnomad4 EAS exome AF: 0.911

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.840

Gnomad4 NFE exome AF: 0.790

Gnomad4 OTH exome AF: 0.762

GnomAD4 genome AF: 0.713 AC: 108352 AN: 151874 Hom.: 40046 Cov.: 35 AF XY: 0.717 AC XY: 53211 AN XY: 74248

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.786

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.715

Alfa AF: 0.684 Hom.: 2195

Bravo AF: 0.705

Asia WGS AF: 0.785 AC: 2725 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Benign	0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs445678; hg19: chr8-26435271; COSMIC: COSV60784646; COSMIC: COSV60784646;