rs11887277

Variant names:

• chr2-26860401-T-C
• rs11887277
• NM_020134.4:c.-5+12147T>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+12147T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,064 control chromosomes in the GnomAD database, including 13,320 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 0.41 (13320 hom., cov: 32)
• Consequence: DPYSL5 NM_020134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020134.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL5	NM_020134.4	MANE Select	c.-5+12147T>C		intron	N/A	NP_064519.2
	DPYSL5	NM_001253723.2		c.-5+12042T>C		intron	N/A	NP_001240652.1	Q9BPU6
	DPYSL5	NM_001253724.2		c.-5+11904T>C		intron	N/A	NP_001240653.1	Q9BPU6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL5	ENST00000288699.11	TSL:1 MANE Select	c.-5+12147T>C		intron	N/A	ENSP00000288699.6	Q9BPU6
	DPYSL5	ENST00000401478.5	TSL:1	c.-5+12042T>C		intron	N/A	ENSP00000385549.1	Q9BPU6
	DPYSL5	ENST00000614712.4	TSL:5	c.-5+11904T>C		intron	N/A	ENSP00000481305.1	Q9BPU6

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62714 AN: 151946 Hom.: 13296 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.413 AC: 62789 AN: 152064 Hom.: 13320 Cov.: 32 AF XY: 0.407 AC XY: 30286 AN XY: 74328

African (AFR) AF: 0.443 AC: 18363 AN: 41456

American (AMR) AF: 0.487 AC: 7448 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1273 AN: 3470

East Asian (EAS) AF: 0.162 AC: 836 AN: 5176

South Asian (SAS) AF: 0.314 AC: 1517 AN: 4824

European-Finnish (FIN) AF: 0.355 AC: 3753 AN: 10580

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28162 AN: 67960

Other (OTH) AF: 0.417 AC: 880 AN: 2112

Alfa AF: 0.422 Hom.: 23833

Bravo AF: 0.427

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.67
PhyloP100		1.7
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: rs11887277; hg19: chr2-27083269;