rs379266

Variant names:

• chr8-26578593-C-A
• rs379266
• NM_001197293.3:c.355-3376C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-26578593-C-A
• chr8-26578593-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001197293.3(DPYSL2):​c.355-3376C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.355-3376C>A		intron_variant	Intron 1 of 13	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.39+300C>A		intron_variant	Intron 1 of 13		NP_001377.1
DPYSL2	NM_001244604.2	c.-70+60C>A		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>A		intron_variant	Intron 1 of 13	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000311151.9	c.39+300C>A		intron_variant	Intron 1 of 13	1		ENSP00000309539.5
DPYSL2	ENST00000523027.1	c.-70+60C>A		intron_variant	Intron 1 of 13	2		ENSP00000431117.1
DPYSL2	ENST00000493789.6	c.255+1226C>A		intron_variant	Intron 1 of 2	4		ENSP00000427954.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1134384 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 543726

African (AFR) AF: 0.00 AC: 0 AN: 23982

American (AMR) AF: 0.00 AC: 0 AN: 10834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14854

East Asian (EAS) AF: 0.00 AC: 0 AN: 22110

South Asian (SAS) AF: 0.00 AC: 0 AN: 47580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2978

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 948198

Other (OTH) AF: 0.00 AC: 0 AN: 45422

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 5507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.5
DANN	Benign	0.86
PhyloP100		0.16
PromoterAI		-0.0013	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;