8-26577755-C-T

Variant names:

• chr8-26577755-C-T
• rs445678
• NM_001197293.3:c.355-4214C>T

Variant summary

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

The NM_001197293.3(DPYSL2):​c.355-4214C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 964,490 control chromosomes in the GnomAD database, including 290,097 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 0.71 (40046 hom., cov: 35)
  • Exomes 𝑓: 0.78 (250051 hom.)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441
• 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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.355-4214C>T		intron_variant	Intron 1 of 13	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.-500C>T		upstream_gene_variant			NP_001377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.355-4214C>T		intron_variant	Intron 1 of 13	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000493789.6	c.255+388C>T		intron_variant	Intron 1 of 2	4		ENSP00000427954.1
DPYSL2	ENST00000311151.9	c.-500C>T		upstream_gene_variant		1		ENSP00000309539.5

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108322 AN: 151766 Hom.: 40041 Cov.: 35

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.716

GnomAD4 exome AF: 0.783 AC: 636124 AN: 812616 Hom.: 250051 AF XY: 0.783 AC XY: 294494 AN XY: 375896

African (AFR) AF: 0.462 AC: 7056 AN: 15278

American (AMR) AF: 0.834 AC: 802 AN: 962

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 3874 AN: 5008

East Asian (EAS) AF: 0.911 AC: 3237 AN: 3554

South Asian (SAS) AF: 0.760 AC: 12275 AN: 16156

European-Finnish (FIN) AF: 0.840 AC: 257 AN: 306

Middle Eastern (MID) AF: 0.705 AC: 1104 AN: 1566

European-Non Finnish (NFE) AF: 0.790 AC: 587131 AN: 743046

Other (OTH) AF: 0.762 AC: 20388 AN: 26740

GnomAD4 genome AF: 0.713 AC: 108352 AN: 151874 Hom.: 40046 Cov.: 35 AF XY: 0.717 AC XY: 53211 AN XY: 74248

African (AFR) AF: 0.501 AC: 20794 AN: 41476

American (AMR) AF: 0.781 AC: 11939 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2700 AN: 3466

East Asian (EAS) AF: 0.930 AC: 4757 AN: 5116

South Asian (SAS) AF: 0.762 AC: 3681 AN: 4830

European-Finnish (FIN) AF: 0.786 AC: 8255 AN: 10508

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.791 AC: 53690 AN: 67890

Other (OTH) AF: 0.715 AC: 1508 AN: 2110

Alfa AF: 0.684 Hom.: 2195

Bravo AF: 0.705

Asia WGS AF: 0.785 AC: 2725 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Benign	0.90
PhyloP100		0.44
PromoterAI		0.0048	Neutral
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: rs445678; hg19: chr8-26435271; COSMIC: COSV60784646; COSMIC: COSV60784646;