8-26641573-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.1127-1866C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,296 control chromosomes in the GnomAD database, including 56,806 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 0.86 (56806 hom., cov: 34)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPYSL2	NM_001197293.3	c.1127-1866C>T		intron_variant		ENST00000521913.7
DPYSL2	NM_001244604.2	c.704-1866C>T		intron_variant
DPYSL2	NM_001386.6	c.812-1866C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYSL2	ENST00000521913.7	c.1127-1866C>T		intron_variant		1	NM_001197293.3

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130977 AN: 152178 Hom.: 56763 Cov.: 34

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.851

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.861 AC: 131070 AN: 152296 Hom.: 56806 Cov.: 34 AF XY: 0.855 AC XY: 63661 AN XY: 74468

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.865

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.877

Gnomad4 OTH AF: 0.849

Alfa AF: 0.857 Hom.: 69587

Bravo AF: 0.848

Asia WGS AF: 0.798 AC: 2771 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.4
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4733048; hg19: chr8-26499089;