8-26610316-G-A

Position:

• chr8-26610316-G-A

Variant summary

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

The NM_001197293.3(DPYSL2):​c.629-13827G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0351 in 152,314 control chromosomes in the GnomAD database, including 148 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 0.035 (148 hom., cov: 33)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.629-13827G>A		intron_variant		ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001244604.2	c.206-13827G>A		intron_variant			NP_001231533.1
DPYSL2	NM_001386.6	c.314-13827G>A		intron_variant			NP_001377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.629-13827G>A		intron_variant		1	NM_001197293.3	ENSP00000427985
DPYSL2	ENST00000311151.9	c.314-13827G>A		intron_variant		1		ENSP00000309539	P1
DPYSL2	ENST00000523027.1	c.206-13827G>A		intron_variant		2		ENSP00000431117

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5342 AN: 152196 Hom.: 148 Cov.: 33

Gnomad AFR AF: 0.00753

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0723

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.0421

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.0320

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

GnomAD4 genome AF: 0.0351 AC: 5345 AN: 152314 Hom.: 148 Cov.: 33 AF XY: 0.0390 AC XY: 2901 AN XY: 74472

Gnomad4 AFR AF: 0.00750

Gnomad4 AMR AF: 0.0727

Gnomad4 ASJ AF: 0.0446

Gnomad4 EAS AF: 0.0922

Gnomad4 SAS AF: 0.0417

Gnomad4 FIN AF: 0.0679

Gnomad4 NFE AF: 0.0331

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0339 Hom.: 92

Bravo AF: 0.0343

Asia WGS AF: 0.0630 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.20
DANN	Benign	0.45

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: rs2585458; hg19: chr8-26467832;