rs7832576

Positions:

• chr8-26629226-A-G

Variant summary

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

The NM_001197293.3(DPYSL2):​c.1005+1286A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,118 control chromosomes in the GnomAD database, including 3,040 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 0.15 (3040 hom., cov: 33)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPYSL2	NM_001197293.3	c.1005+1286A>G		intron_variant		ENST00000521913.7
DPYSL2	NM_001244604.2	c.582+1286A>G		intron_variant
DPYSL2	NM_001386.6	c.690+1286A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYSL2	ENST00000521913.7	c.1005+1286A>G		intron_variant		1	NM_001197293.3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22480 AN: 152000 Hom.: 3026 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.148 AC: 22542 AN: 152118 Hom.: 3040 Cov.: 33 AF XY: 0.144 AC XY: 10697 AN XY: 74382

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0344

Gnomad4 NFE AF: 0.0653

Gnomad4 OTH AF: 0.162

Alfa AF: 0.0770 Hom.: 436

Bravo AF: 0.161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7832576; hg19: chr8-26486742;