chr8-26584046-A-G

Variant names:

• chr8-26584046-A-G
• rs408753
• NM_001197293.3:c.628+63A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001197293.3(DPYSL2):​c.628+63A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,510,950 control chromosomes in the GnomAD database, including 89,878 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 0.40 (13338 hom., cov: 32)
  • Exomes 𝑓: 0.33 (76540 hom.)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.628+63A>G		intron_variant	Intron 3 of 13	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.313+63A>G		intron_variant	Intron 3 of 13		NP_001377.1
DPYSL2	NM_001244604.2	c.205+63A>G		intron_variant	Intron 3 of 13		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.628+63A>G		intron_variant	Intron 3 of 13	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000311151.9	c.313+63A>G		intron_variant	Intron 3 of 13	1		ENSP00000309539.5
DPYSL2	ENST00000523027.1	c.205+63A>G		intron_variant	Intron 3 of 13	2		ENSP00000431117.1
DPYSL2	ENST00000493789.6	c.*81A>G		downstream_gene_variant		4		ENSP00000427954.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60448 AN: 151908 Hom.: 13303 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.328 AC: 446382 AN: 1358924 Hom.: 76540 AF XY: 0.333 AC XY: 224169 AN XY: 672750

African (AFR) AF: 0.607 AC: 18532 AN: 30518

American (AMR) AF: 0.299 AC: 10888 AN: 36472

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 7721 AN: 22080

East Asian (EAS) AF: 0.254 AC: 9633 AN: 37930

South Asian (SAS) AF: 0.505 AC: 37840 AN: 74888

European-Finnish (FIN) AF: 0.306 AC: 15672 AN: 51158

Middle Eastern (MID) AF: 0.385 AC: 1896 AN: 4920

European-Non Finnish (NFE) AF: 0.311 AC: 325143 AN: 1044708

Other (OTH) AF: 0.339 AC: 19057 AN: 56250

GnomAD4 genome AF: 0.398 AC: 60533 AN: 152026 Hom.: 13338 Cov.: 32 AF XY: 0.399 AC XY: 29676 AN XY: 74330

African (AFR) AF: 0.599 AC: 24821 AN: 41446

American (AMR) AF: 0.334 AC: 5107 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1221 AN: 3472

East Asian (EAS) AF: 0.239 AC: 1234 AN: 5170

South Asian (SAS) AF: 0.526 AC: 2531 AN: 4808

European-Finnish (FIN) AF: 0.308 AC: 3248 AN: 10554

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21202 AN: 67978

Other (OTH) AF: 0.367 AC: 772 AN: 2106

Alfa AF: 0.351 Hom.: 2922

Bravo AF: 0.402

Asia WGS AF: 0.382 AC: 1331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.64
PhyloP100		-0.39
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: rs408753; hg19: chr8-26441562;