chr8-26578593-C-T

Position:

• chr8-26578593-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.355-3376C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 1,285,688 control chromosomes in the GnomAD database, including 398,179 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 0.76 (43908 hom., cov: 31)
  • Exomes 𝑓: 0.79 (354271 hom.)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.355-3376C>T		intron_variant		ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.39+300C>T		intron_variant			NP_001377.1
DPYSL2	NM_001244604.2	c.-70+60C>T		intron_variant			NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.355-3376C>T		intron_variant		1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000311151.9	c.39+300C>T		intron_variant		1		ENSP00000309539.5
DPYSL2	ENST00000523027.1	c.-70+60C>T		intron_variant		2		ENSP00000431117.1
DPYSL2	ENST00000493789.6	c.255+1226C>T		intron_variant		4		ENSP00000427954.1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114979 AN: 151902 Hom.: 43886 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.747

GnomAD4 exome AF: 0.790 AC: 895206 AN: 1133668 Hom.: 354271 AF XY: 0.789 AC XY: 428559 AN XY: 543386

Gnomad4 AFR exome AF: 0.643

Gnomad4 AMR exome AF: 0.841

Gnomad4 ASJ exome AF: 0.779

Gnomad4 EAS exome AF: 0.935

Gnomad4 SAS exome AF: 0.755

Gnomad4 FIN exome AF: 0.786

Gnomad4 NFE exome AF: 0.792

Gnomad4 OTH exome AF: 0.778

GnomAD4 genome AF: 0.757 AC: 115049 AN: 152020 Hom.: 43908 Cov.: 31 AF XY: 0.758 AC XY: 56295 AN XY: 74300

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.745

Alfa AF: 0.773 Hom.: 5345

Bravo AF: 0.756

Asia WGS AF: 0.794 AC: 2761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.1
DANN	Benign	0.89

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: rs379266; hg19: chr8-26436109;