rs3837184

Variant names:

• chr8-26577992-CT-C
• rs3837184
• ENST00000311151.9:c.-261delT

Your query was ambiguous. Multiple possible variants found:

• chr8-26577992-CT-C
• chr8-26577992-CT-CTT
• chr8-26577992-CT-CTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000311151.9(DPYSL2):​c.-261delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000086 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPYSL2 ENST00000311151.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.355-3975delT		intron_variant	Intron 1 of 13	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.-261delT		5_prime_UTR_variant	Exon 1 of 14		NP_001377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000311151.9	c.-261delT		5_prime_UTR_variant	Exon 1 of 14	1		ENSP00000309539.5
DPYSL2	ENST00000521913.7	c.355-3975delT		intron_variant	Intron 1 of 13	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000493789.6	c.255+627delT		intron_variant	Intron 1 of 2	4		ENSP00000427954.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000865 AC: 10 AN: 1156708 Hom.: 0 Cov.: 51 AF XY: 0.00000717 AC XY: 4 AN XY: 557534

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24214

American (AMR) AF: 0.00 AC: 0 AN: 12690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15252

East Asian (EAS) AF: 0.00 AC: 0 AN: 23920

South Asian (SAS) AF: 0.00 AC: 0 AN: 54154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3098

European-Non Finnish (NFE) AF: 0.0000104 AC: 10 AN: 959676

Other (OTH) AF: 0.00 AC: 0 AN: 45766

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.041

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: rs3837184; hg19: chr8-26435508;