rs388047

Variant names:

• chr8-26582713-G-A
• rs388047
• NM_001197293.3:c.443+656G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-26582713-G-A
• chr8-26582713-G-C
• chr8-26582713-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.443+656G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,968 control chromosomes in the GnomAD database, including 13,311 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 (13311 hom., cov: 32)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.443+656G>A		intron_variant	Intron 2 of 13	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.128+656G>A		intron_variant	Intron 2 of 13		NP_001377.1
DPYSL2	NM_001244604.2	c.20+656G>A		intron_variant	Intron 2 of 13		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.443+656G>A		intron_variant	Intron 2 of 13	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000311151.9	c.128+656G>A		intron_variant	Intron 2 of 13	1		ENSP00000309539.5
DPYSL2	ENST00000523027.1	c.20+656G>A		intron_variant	Intron 2 of 13	2		ENSP00000431117.1
DPYSL2	ENST00000493789.6	c.344+656G>A		intron_variant	Intron 2 of 2	4		ENSP00000427954.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60386 AN: 151850 Hom.: 13276 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.398 AC: 60471 AN: 151968 Hom.: 13311 Cov.: 32 AF XY: 0.399 AC XY: 29643 AN XY: 74302

African (AFR) AF: 0.599 AC: 24808 AN: 41434

American (AMR) AF: 0.334 AC: 5101 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3468

East Asian (EAS) AF: 0.239 AC: 1237 AN: 5168

South Asian (SAS) AF: 0.526 AC: 2533 AN: 4816

European-Finnish (FIN) AF: 0.307 AC: 3234 AN: 10536

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

European-Non Finnish (NFE) AF: 0.312 AC: 21168 AN: 67950

Other (OTH) AF: 0.367 AC: 775 AN: 2114

Alfa AF: 0.343 Hom.: 26507

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	-0.82
CADD	Benign	10
DANN	Benign	0.44
PhyloP100		1.1
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: rs388047; hg19: chr8-26440229;