8-26657622-C-T

Position:

• chr8-26657622-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001197293.3(DPYSL2):​c.*1916C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 152,460 control chromosomes in the GnomAD database, including 624 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 0.088 (618 hom., cov: 33)
  • Exomes 𝑓: 0.14 (6 hom.)
• Consequence: DPYSL2 NM_001197293.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.*1916C>T		3_prime_UTR_variant	14/14	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.*1916C>T		3_prime_UTR_variant	14/14		NP_001377.1
DPYSL2	NM_001244604.2	c.*1916C>T		3_prime_UTR_variant	14/14		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.*1916C>T		3_prime_UTR_variant	14/14	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000311151.9	c.*1916C>T		3_prime_UTR_variant	14/14	1		ENSP00000309539.5

Frequencies

GnomAD3 genomes AF: 0.0883 AC: 13409 AN: 151912 Hom.: 618 Cov.: 33

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0758

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0972

Gnomad OTH AF: 0.0742

GnomAD4 exome AF: 0.137 AC: 59 AN: 430 Hom.: 6 Cov.: 0 AF XY: 0.150 AC XY: 39 AN XY: 260

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0882 AC: 13411 AN: 152030 Hom.: 618 Cov.: 33 AF XY: 0.0888 AC XY: 6596 AN XY: 74306

Gnomad4 AFR AF: 0.0726

Gnomad4 AMR AF: 0.0560

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.0759

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0972

Gnomad4 OTH AF: 0.0739

Alfa AF: 0.0907 Hom.: 126

Bravo AF: 0.0830

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.78

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: rs45471201; hg19: chr8-26515138;