chr8-26624306-C-T

Variant names:

• chr8-26624306-C-T
• rs139123217
• NM_001197293.3:c.792C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001197293.3(DPYSL2):​c.792C>T​(p.His264His) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,613,984 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (12 hom.)
• Consequence: DPYSL2 NM_001197293.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.002138
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.702
• Publications: 5 publications found

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]

DPYSL2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 8-26624306-C-T is Benign according to our data. Variant chr8-26624306-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 718924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.702 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 12 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197293.3. 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
	DPYSL2	NM_001197293.3	MANE Select	c.792C>T	p.His264His	splice_region synonymous	Exon 4 of 14	NP_001184222.1	A0A1C7CYX9
	DPYSL2	NM_001386.6		c.477C>T	p.His159His	splice_region synonymous	Exon 4 of 14	NP_001377.1	Q16555-1
	DPYSL2	NM_001244604.2		c.369C>T	p.His123His	splice_region synonymous	Exon 4 of 14	NP_001231533.1	Q16555-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL2	ENST00000521913.7	TSL:1 MANE Select	c.792C>T	p.His264His	splice_region synonymous	Exon 4 of 14	ENSP00000427985.2	A0A1C7CYX9
	DPYSL2	ENST00000311151.9	TSL:1	c.477C>T	p.His159His	splice_region synonymous	Exon 4 of 14	ENSP00000309539.5	Q16555-1
	DPYSL2	ENST00000523027.1	TSL:2	c.369C>T	p.His123His	splice_region synonymous	Exon 4 of 14	ENSP00000431117.1	Q16555-2

Frequencies

GnomAD3 genomes AF: 0.00291 AC: 443 AN: 152210 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00434

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00319 AC: 800 AN: 250758 AF XY: 0.00321

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.00997

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00458

Gnomad NFE exome AF: 0.00415

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00377 AC: 5508 AN: 1461656 Hom.: 12 Cov.: 33 AF XY: 0.00366 AC XY: 2664 AN XY: 727110

African (AFR) AF: 0.000358 AC: 12 AN: 33480

American (AMR) AF: 0.00266 AC: 119 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00981 AC: 256 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000429 AC: 37 AN: 86222

European-Finnish (FIN) AF: 0.00421 AC: 225 AN: 53414

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.00417 AC: 4638 AN: 1111882

Other (OTH) AF: 0.00359 AC: 217 AN: 60386

GnomAD4 genome AF: 0.00291 AC: 444 AN: 152328 Hom.: 1 Cov.: 32 AF XY: 0.00271 AC XY: 202 AN XY: 74486

African (AFR) AF: 0.000337 AC: 14 AN: 41578

American (AMR) AF: 0.00222 AC: 34 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00414 AC: 44 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00434 AC: 295 AN: 68026

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00365 Hom.: 4

Bravo AF: 0.00260

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00387

EpiControl AF: 0.00480

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.7
DANN	Benign	0.67
PhyloP100		-0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0021
dbscSNV1_RF	Benign	0.064
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: rs139123217; hg19: chr8-26481822;