8-26579060-G-C

Variant names:

• chr8-26579060-G-C
• rs11781865
• NM_001197293.3:c.355-2909G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001197293.3(DPYSL2):​c.355-2909G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,230 control chromosomes in the GnomAD database, including 1,365 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 0.13 (1365 hom., cov: 34)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.355-2909G>C		intron_variant	Intron 1 of 13	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.39+767G>C		intron_variant	Intron 1 of 13		NP_001377.1
DPYSL2	NM_001244604.2	c.-70+527G>C		intron_variant	Intron 1 of 13		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.355-2909G>C		intron_variant	Intron 1 of 13	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000311151.9	c.39+767G>C		intron_variant	Intron 1 of 13	1		ENSP00000309539.5
DPYSL2	ENST00000523027.1	c.-70+527G>C		intron_variant	Intron 1 of 13	2		ENSP00000431117.1
DPYSL2	ENST00000493789.6	c.255+1693G>C		intron_variant	Intron 1 of 2	4		ENSP00000427954.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19803 AN: 152112 Hom.: 1361 Cov.: 34

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0504

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.130 AC: 19829 AN: 152230 Hom.: 1365 Cov.: 34 AF XY: 0.127 AC XY: 9491 AN XY: 74442

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0509

Gnomad4 SAS AF: 0.0902

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.149

Alfa AF: 0.0528 Hom.: 57

Bravo AF: 0.132

Asia WGS AF: 0.0690 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.63

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: rs11781865; hg19: chr8-26436576;