rs367948

Variant names:

• chr8-26577600-G-C
• rs367948
• NM_001197293.3:c.355-4369G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-26577600-G-C
• chr8-26577600-G-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.355-4369G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 148,458 control chromosomes in the GnomAD database, including 42,843 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 (42843 hom., cov: 29)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 6 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=-0.84).
• 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.355-4369G>C		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.355-4369G>C		intron_variant	Intron 1 of 13	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000493789.6	c.255+233G>C		intron_variant	Intron 1 of 2	4		ENSP00000427954.1
DPYSL2	ENST00000311151.9	c.-655G>C		upstream_gene_variant		1		ENSP00000309539.5

Frequencies

GnomAD3 genomes AF: 0.757 AC: 112249 AN: 148360 Hom.: 42826 Cov.: 29

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.756 AC: 112305 AN: 148458 Hom.: 42843 Cov.: 29 AF XY: 0.758 AC XY: 54890 AN XY: 72450

African (AFR) AF: 0.650 AC: 26366 AN: 40542

American (AMR) AF: 0.797 AC: 11985 AN: 15034

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2679 AN: 3442

East Asian (EAS) AF: 0.929 AC: 4628 AN: 4980

South Asian (SAS) AF: 0.763 AC: 3660 AN: 4796

European-Finnish (FIN) AF: 0.787 AC: 7576 AN: 9630

Middle Eastern (MID) AF: 0.764 AC: 220 AN: 288

European-Non Finnish (NFE) AF: 0.791 AC: 52850 AN: 66774

Other (OTH) AF: 0.743 AC: 1539 AN: 2070

Alfa AF: 0.726 Hom.: 2415

Bravo AF: 0.757

Asia WGS AF: 0.786 AC: 2422 AN: 3082

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.34
PhyloP100		-1.0
PromoterAI		-0.070	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: rs367948; hg19: chr8-26435116;