8-26566664-T-C

Variant names:

• chr8-26566664-T-C
• rs424138
• NM_001197293.3:c.355-15305T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001197293.3(DPYSL2):​c.355-15305T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 151,988 control chromosomes in the GnomAD database, including 46,385 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 0.78 (46385 hom., cov: 30)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• Publications: 4 publications found

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]

DPYSL2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL2	NM_001197293.3	MANE Select	c.355-15305T>C		intron	N/A	NP_001184222.1	A0A1C7CYX9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL2	ENST00000521913.7	TSL:1 MANE Select	c.355-15305T>C		intron	N/A	ENSP00000427985.2	A0A1C7CYX9

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118303 AN: 151870 Hom.: 46337 Cov.: 30

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.779 AC: 118406 AN: 151988 Hom.: 46385 Cov.: 30 AF XY: 0.779 AC XY: 57897 AN XY: 74278

African (AFR) AF: 0.735 AC: 30419 AN: 41408

American (AMR) AF: 0.834 AC: 12745 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2918 AN: 3470

East Asian (EAS) AF: 0.980 AC: 5041 AN: 5144

South Asian (SAS) AF: 0.687 AC: 3307 AN: 4812

European-Finnish (FIN) AF: 0.795 AC: 8413 AN: 10580

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.779 AC: 52925 AN: 67974

Other (OTH) AF: 0.783 AC: 1653 AN: 2110

Alfa AF: 0.780 Hom.: 56837

Bravo AF: 0.786

Asia WGS AF: 0.814 AC: 2828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.3
DANN	Benign	0.70
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs424138; hg19: chr8-26424180;