rs388047

Positions:

• chr8-26582713-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.443+656G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,968 control chromosomes in the GnomAD database, including 13,311 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 0.40 (13311 hom., cov: 32)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.443+656G>A		intron_variant		ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001244604.2	c.20+656G>A		intron_variant			NP_001231533.1
DPYSL2	NM_001386.6	c.128+656G>A		intron_variant			NP_001377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.443+656G>A		intron_variant		1	NM_001197293.3	ENSP00000427985
DPYSL2	ENST00000311151.9	c.128+656G>A		intron_variant		1		ENSP00000309539	P1
DPYSL2	ENST00000493789.6	c.344+656G>A		intron_variant		4		ENSP00000427954
DPYSL2	ENST00000523027.1	c.20+656G>A		intron_variant		2		ENSP00000431117

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60386 AN: 151850 Hom.: 13276 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.398 AC: 60471 AN: 151968 Hom.: 13311 Cov.: 32 AF XY: 0.399 AC XY: 29643 AN XY: 74302

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.367

Alfa AF: 0.325 Hom.: 13841

Bravo AF: 0.402

Asia WGS AF: 0.382 AC: 1331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.44

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: rs388047; hg19: chr8-26440229;