8-26578593-C-T

Variant names:

• chr8-26578593-C-T
• rs379266
• NM_001197293.3:c.355-3376C>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.355-3376C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 1,285,688 control chromosomes in the GnomAD database, including 398,179 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 0.76 (43908 hom., cov: 31)
  • Exomes 𝑓: 0.79 (354271 hom.)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 1 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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.355-3376C>T		intron_variant	Intron 1 of 13	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.39+300C>T		intron_variant	Intron 1 of 13		NP_001377.1
DPYSL2	NM_001244604.2	c.-70+60C>T		intron_variant	Intron 1 of 13		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.355-3376C>T		intron_variant	Intron 1 of 13	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000311151.9	c.39+300C>T		intron_variant	Intron 1 of 13	1		ENSP00000309539.5
DPYSL2	ENST00000523027.1	c.-70+60C>T		intron_variant	Intron 1 of 13	2		ENSP00000431117.1
DPYSL2	ENST00000493789.6	c.255+1226C>T		intron_variant	Intron 1 of 2	4		ENSP00000427954.1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 114979 AN: 151902 Hom.: 43886 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.779

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.747

GnomAD4 exome AF: 0.790 AC: 895206 AN: 1133668 Hom.: 354271 AF XY: 0.789 AC XY: 428559 AN XY: 543386

African (AFR) AF: 0.643 AC: 15402 AN: 23958

American (AMR) AF: 0.841 AC: 9089 AN: 10806

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 11556 AN: 14828

East Asian (EAS) AF: 0.935 AC: 20667 AN: 22100

South Asian (SAS) AF: 0.755 AC: 35865 AN: 47522

European-Finnish (FIN) AF: 0.786 AC: 14439 AN: 18368

Middle Eastern (MID) AF: 0.721 AC: 2147 AN: 2976

European-Non Finnish (NFE) AF: 0.792 AC: 750761 AN: 947738

Other (OTH) AF: 0.778 AC: 35280 AN: 45372

GnomAD4 genome AF: 0.757 AC: 115049 AN: 152020 Hom.: 43908 Cov.: 31 AF XY: 0.758 AC XY: 56295 AN XY: 74300

African (AFR) AF: 0.652 AC: 26981 AN: 41404

American (AMR) AF: 0.798 AC: 12197 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 2703 AN: 3470

East Asian (EAS) AF: 0.929 AC: 4793 AN: 5160

South Asian (SAS) AF: 0.760 AC: 3667 AN: 4822

European-Finnish (FIN) AF: 0.775 AC: 8179 AN: 10560

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53924 AN: 68006

Other (OTH) AF: 0.745 AC: 1571 AN: 2108

Alfa AF: 0.767 Hom.: 5507

Bravo AF: 0.756

Asia WGS AF: 0.794 AC: 2761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.1
DANN	Benign	0.89
PhyloP100		0.16
PromoterAI		0.089	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs379266; hg19: chr8-26436109;