chr8-26577607-C-T

Variant names:

• chr8-26577607-C-T
• rs400181
• NM_001197293.3:c.355-4362C>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.355-4362C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 148,826 control chromosomes in the GnomAD database, including 39,187 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 (39187 hom., cov: 30)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• 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=-0.82).
• 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.355-4362C>T		intron_variant	Intron 1 of 13	ENST00000521913.7	NP_001184222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.355-4362C>T		intron_variant	Intron 1 of 13	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000493789.6	c.255+240C>T		intron_variant	Intron 1 of 2	4		ENSP00000427954.1
DPYSL2	ENST00000311151.9	c.-648C>T		upstream_gene_variant		1		ENSP00000309539.5

Frequencies

GnomAD3 genomes AF: 0.713 AC: 106019 AN: 148724 Hom.: 39184 Cov.: 30

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.713 AC: 106045 AN: 148826 Hom.: 39187 Cov.: 30 AF XY: 0.716 AC XY: 51965 AN XY: 72626

African (AFR) AF: 0.500 AC: 20368 AN: 40746

American (AMR) AF: 0.780 AC: 11748 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2684 AN: 3448

East Asian (EAS) AF: 0.930 AC: 4628 AN: 4978

South Asian (SAS) AF: 0.762 AC: 3662 AN: 4808

European-Finnish (FIN) AF: 0.787 AC: 7600 AN: 9662

Middle Eastern (MID) AF: 0.745 AC: 216 AN: 290

European-Non Finnish (NFE) AF: 0.790 AC: 52857 AN: 66868

Other (OTH) AF: 0.714 AC: 1482 AN: 2076

Alfa AF: 0.743 Hom.: 5212

Bravo AF: 0.707

Asia WGS AF: 0.772 AC: 2389 AN: 3094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.077
PromoterAI		0.040	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: rs400181; hg19: chr8-26435123;