NM_020134.4:c.670-1634C>T

Variant names:

• chr2-26930006-C-T
• rs1371614
• NM_020134.4:c.670-1634C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020134.4(DPYSL5):​c.670-1634C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,040 control chromosomes in the GnomAD database, including 6,672 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 0.29 (6672 hom., cov: 33)
• Consequence: DPYSL5 NM_020134.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450
• Publications: 41 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.356 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL5	NM_020134.4	MANE Select	c.670-1634C>T		intron	N/A	NP_064519.2
	DPYSL5	NM_001253723.2		c.670-1634C>T		intron	N/A	NP_001240652.1
	DPYSL5	NM_001253724.2		c.670-1634C>T		intron	N/A	NP_001240653.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL5	ENST00000288699.11	TSL:1 MANE Select	c.670-1634C>T		intron	N/A	ENSP00000288699.6
	DPYSL5	ENST00000401478.5	TSL:1	c.670-1634C>T		intron	N/A	ENSP00000385549.1
	DPYSL5	ENST00000614712.4	TSL:5	c.670-1634C>T		intron	N/A	ENSP00000481305.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43354 AN: 151922 Hom.: 6652 Cov.: 33

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.285 AC: 43407 AN: 152040 Hom.: 6672 Cov.: 33 AF XY: 0.282 AC XY: 20935 AN XY: 74320

African (AFR) AF: 0.360 AC: 14910 AN: 41430

American (AMR) AF: 0.363 AC: 5560 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 775 AN: 3458

East Asian (EAS) AF: 0.155 AC: 804 AN: 5178

South Asian (SAS) AF: 0.217 AC: 1043 AN: 4816

European-Finnish (FIN) AF: 0.206 AC: 2184 AN: 10586

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17158 AN: 67964

Other (OTH) AF: 0.271 AC: 571 AN: 2110

Alfa AF: 0.265 Hom.: 22643

Bravo AF: 0.305

Asia WGS AF: 0.201 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-0.45
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: rs1371614; hg19: chr2-27152874;