rs6756245

Positions:

• chr2-26860621-T-C

Variant summary

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

The NM_020134.4(DPYSL5):​c.-5+12367T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,048 control chromosomes in the GnomAD database, including 12,133 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 0.39 (12133 hom., cov: 32)
• Consequence: DPYSL5 NM_020134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.752

Genes affected

DPYSL5 (HGNC:20637): (dihydropyrimidinase like 5) This gene encodes a member of the CRMP (collapsing response mediator protein) family thought to be involved in neural development. Antibodies to the encoded protein were found in some patients with neurologic symptoms who had paraneoplastic syndrome. A pseudogene of this gene is found on chromosome 11. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYSL5	NM_020134.4	c.-5+12367T>C		intron_variant		ENST00000288699.11	NP_064519.2
DPYSL5	NM_001253723.2	c.-5+12262T>C		intron_variant			NP_001240652.1
DPYSL5	NM_001253724.2	c.-5+12124T>C		intron_variant			NP_001240653.1
DPYSL5	XM_024453007.2	c.-5+11121T>C		intron_variant			XP_024308775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL5	ENST00000288699.11	c.-5+12367T>C		intron_variant		1	NM_020134.4	ENSP00000288699	P1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59932 AN: 151930 Hom.: 12114 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.395 AC: 59996 AN: 152048 Hom.: 12133 Cov.: 32 AF XY: 0.390 AC XY: 28984 AN XY: 74336

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.405

Alfa AF: 0.413 Hom.: 27105

Bravo AF: 0.406

Asia WGS AF: 0.268 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.9
DANN	Benign	0.84

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: rs6756245; hg19: chr2-27083489;