NM_001197293.3:c.628+11606T>C

Variant names:

• chr8-26595589-T-C
• rs5029306
• NM_001197293.3:c.628+11606T>C

Variant summary

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

The NM_001197293.3(DPYSL2):​c.628+11606T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,090 control chromosomes in the GnomAD database, including 27,161 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 0.59 (27161 hom., cov: 33)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.628+11606T>C		intron_variant	Intron 3 of 13	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.313+11606T>C		intron_variant	Intron 3 of 13		NP_001377.1
DPYSL2	NM_001244604.2	c.205+11606T>C		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+11606T>C		intron_variant	Intron 3 of 13	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000311151.9	c.313+11606T>C		intron_variant	Intron 3 of 13	1		ENSP00000309539.5
DPYSL2	ENST00000523027.1	c.205+11606T>C		intron_variant	Intron 3 of 13	2		ENSP00000431117.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89045 AN: 151974 Hom.: 27143 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.586 AC: 89105 AN: 152090 Hom.: 27161 Cov.: 33 AF XY: 0.589 AC XY: 43779 AN XY: 74332

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.593

Alfa AF: 0.631 Hom.: 28415

Bravo AF: 0.580

Asia WGS AF: 0.636 AC: 2208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.53
DANN	Benign	0.35

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: rs5029306; hg19: chr8-26453105;