8-26634954-G-T

Variant names:

• chr8-26634954-G-T
• rs55906521
• NM_001197293.3:c.1126+54G>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.1126+54G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.072 in 1,607,428 control chromosomes in the GnomAD database, including 4,930 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 0.068 (454 hom., cov: 31)
  • Exomes 𝑓: 0.072 (4476 hom.)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 4 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=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL2	NM_001197293.3	MANE Select	c.1126+54G>T		intron	N/A	NP_001184222.1
	DPYSL2	NM_001386.6		c.811+54G>T		intron	N/A	NP_001377.1
	DPYSL2	NM_001244604.2		c.703+54G>T		intron	N/A	NP_001231533.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL2	ENST00000521913.7	TSL:1 MANE Select	c.1126+54G>T		intron	N/A	ENSP00000427985.2
	DPYSL2	ENST00000311151.9	TSL:1	c.811+54G>T		intron	N/A	ENSP00000309539.5
	DPYSL2	ENST00000523027.1	TSL:2	c.703+54G>T		intron	N/A	ENSP00000431117.1

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10425 AN: 152138 Hom.: 458 Cov.: 31

Gnomad AFR AF: 0.0669

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0643

Gnomad ASJ AF: 0.0977

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0808

GnomAD4 exome AF: 0.0723 AC: 105262 AN: 1455172 Hom.: 4476 AF XY: 0.0750 AC XY: 54223 AN XY: 723120

African (AFR) AF: 0.0672 AC: 2244 AN: 33386

American (AMR) AF: 0.0499 AC: 2217 AN: 44432

Ashkenazi Jewish (ASJ) AF: 0.0947 AC: 2451 AN: 25880

East Asian (EAS) AF: 0.00460 AC: 182 AN: 39548

South Asian (SAS) AF: 0.140 AC: 12026 AN: 85734

European-Finnish (FIN) AF: 0.0301 AC: 1577 AN: 52396

Middle Eastern (MID) AF: 0.126 AC: 725 AN: 5734

European-Non Finnish (NFE) AF: 0.0716 AC: 79335 AN: 1107986

Other (OTH) AF: 0.0750 AC: 4505 AN: 60076

GnomAD4 genome AF: 0.0684 AC: 10420 AN: 152256 Hom.: 454 Cov.: 31 AF XY: 0.0691 AC XY: 5142 AN XY: 74430

African (AFR) AF: 0.0668 AC: 2778 AN: 41556

American (AMR) AF: 0.0642 AC: 982 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0977 AC: 339 AN: 3470

East Asian (EAS) AF: 0.00464 AC: 24 AN: 5170

South Asian (SAS) AF: 0.150 AC: 721 AN: 4818

European-Finnish (FIN) AF: 0.0296 AC: 314 AN: 10616

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0732 AC: 4981 AN: 68004

Other (OTH) AF: 0.0804 AC: 170 AN: 2114

Alfa AF: 0.0186 Hom.: 10

Bravo AF: 0.0686

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.0
DANN	Benign	0.89
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs55906521; hg19: chr8-26492470; COSMIC: COSV107321358; COSMIC: COSV107321358;