2-26860621-T-C

Variant names:

• chr2-26860621-T-C
• rs6756245
• NM_020134.4:c.-5+12367T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

DPYSL5 Gene-Disease associations (from GenCC):

• Ritscher-Schinzel syndrome 4

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DPYSL5	NM_020134.4	c.-5+12367T>C		intron_variant	Intron 1 of 12	ENST00000288699.11	NP_064519.2
DPYSL5	NM_001253723.2	c.-5+12262T>C		intron_variant	Intron 1 of 12		NP_001240652.1
DPYSL5	NM_001253724.2	c.-5+12124T>C		intron_variant	Intron 1 of 12		NP_001240653.1
DPYSL5	XM_024453007.2	c.-5+11121T>C		intron_variant	Intron 1 of 12		XP_024308775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL5	ENST00000288699.11	c.-5+12367T>C		intron_variant	Intron 1 of 12	1	NM_020134.4	ENSP00000288699.6

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

African (AFR) AF: 0.379 AC: 15722 AN: 41442

American (AMR) AF: 0.481 AC: 7346 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1268 AN: 3472

East Asian (EAS) AF: 0.162 AC: 839 AN: 5170

South Asian (SAS) AF: 0.314 AC: 1517 AN: 4826

European-Finnish (FIN) AF: 0.355 AC: 3758 AN: 10572

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.414 AC: 28138 AN: 67960

Other (OTH) AF: 0.405 AC: 857 AN: 2114

Alfa AF: 0.412 Hom.: 41205

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
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6756245; hg19: chr2-27083489;