8-26634954-G-T

Variant names:

• chr8-26634954-G-T
• rs55906521
• NM_001197293.3:c.1126+54G>T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.1126+54G>T		intron_variant	Intron 8 of 13	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.811+54G>T		intron_variant	Intron 8 of 13		NP_001377.1
DPYSL2	NM_001244604.2	c.703+54G>T		intron_variant	Intron 8 of 13		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.1126+54G>T		intron_variant	Intron 8 of 13	1	NM_001197293.3	ENSP00000427985.2

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

Gnomad4 AFR exome AF: 0.0672

Gnomad4 AMR exome AF: 0.0499

Gnomad4 ASJ exome AF: 0.0947

Gnomad4 EAS exome AF: 0.00460

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.0301

Gnomad4 NFE exome AF: 0.0716

Gnomad4 OTH exome AF: 0.0750

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

Gnomad4 AFR AF: 0.0668

Gnomad4 AMR AF: 0.0642

Gnomad4 ASJ AF: 0.0977

Gnomad4 EAS AF: 0.00464

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0296

Gnomad4 NFE AF: 0.0732

Gnomad4 OTH AF: 0.0804

Alfa AF: 0.0169 Hom.: 9

Bravo AF: 0.0686

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.0
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs55906521; hg19: chr8-26492470;