8-26628739-C-T

Variant names:

• chr8-26628739-C-T
• rs11995227
• NM_001197293.3:c.1005+799C>T

Variant summary

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

The NM_001197293.3(DPYSL2):​c.1005+799C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,034 control chromosomes in the GnomAD database, including 4,545 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 0.21 (4545 hom., cov: 32)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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 = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.1005+799C>T		intron_variant	Intron 7 of 13	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.690+799C>T		intron_variant	Intron 7 of 13		NP_001377.1
DPYSL2	NM_001244604.2	c.582+799C>T		intron_variant	Intron 7 of 13		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.1005+799C>T		intron_variant	Intron 7 of 13	1	NM_001197293.3	ENSP00000427985.2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32054 AN: 151916 Hom.: 4535 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.211 AC: 32110 AN: 152034 Hom.: 4545 Cov.: 32 AF XY: 0.208 AC XY: 15481 AN XY: 74324

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.0671

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.238

Alfa AF: 0.149 Hom.: 1914

Bravo AF: 0.223

Asia WGS AF: 0.228 AC: 792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.35

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: rs11995227; hg19: chr8-26486255;