rs10042

Positions:

• chr8-26658147-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001197293.3(DPYSL2):​c.*2441G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 152,550 control chromosomes in the GnomAD database, including 14 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 0.011 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0092 (0 hom.)
• Consequence: DPYSL2 NM_001197293.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262

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=-0.51).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0115 (1748/152116) while in subpopulation NFE AF= 0.0174 (1185/68002). AF 95% confidence interval is 0.0166. There are 14 homozygotes in gnomad4. There are 822 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1748 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.*2441G>A		3_prime_UTR_variant	14/14	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.*2441G>A		3_prime_UTR_variant	14/14		NP_001377.1
DPYSL2	NM_001244604.2	c.*2441G>A		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.*2441G>A		3_prime_UTR_variant	14/14	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000311151.9	c.*2441G>A		3_prime_UTR_variant	14/14	1		ENSP00000309539.5

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1750 AN: 151998 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00353

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.00529

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00922 AC: 4 AN: 434 Hom.: 0 Cov.: 0 AF XY: 0.00769 AC XY: 2 AN XY: 260

Gnomad4 FIN exome AF: 0.00935

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0115 AC: 1748 AN: 152116 Hom.: 14 Cov.: 32 AF XY: 0.0111 AC XY: 822 AN XY: 74386

Gnomad4 AFR AF: 0.00352

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0131

Gnomad4 FIN AF: 0.00529

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0129 Hom.: 4

Bravo AF: 0.0118

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.82

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: rs10042; hg19: chr8-26515663;