8-26626668-C-T

Variant names:

• chr8-26626668-C-T
• rs202167869
• NM_001197293.3:c.845C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001197293.3(DPYSL2):​c.845C>T​(p.Thr282Met) variant causes a missense change. The variant allele was found at a frequency of 0.000169 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: DPYSL2 NM_001197293.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• Publications: 4 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29038733).

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.845C>T	p.Thr282Met	missense	Exon 5 of 14	NP_001184222.1	A0A1C7CYX9
	DPYSL2	NM_001386.6		c.530C>T	p.Thr177Met	missense	Exon 5 of 14	NP_001377.1	Q16555-1
	DPYSL2	NM_001244604.2		c.422C>T	p.Thr141Met	missense	Exon 5 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.845C>T	p.Thr282Met	missense	Exon 5 of 14	ENSP00000427985.2	A0A1C7CYX9
	DPYSL2	ENST00000311151.9	TSL:1	c.530C>T	p.Thr177Met	missense	Exon 5 of 14	ENSP00000309539.5	Q16555-1
	DPYSL2	ENST00000523027.1	TSL:2	c.422C>T	p.Thr141Met	missense	Exon 5 of 14	ENSP00000431117.1	Q16555-2

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000175 AC: 44 AN: 251450 AF XY: 0.000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000176 AC: 258 AN: 1461852 Hom.: 0 Cov.: 31 AF XY: 0.000169 AC XY: 123 AN XY: 727234

African (AFR) AF: 0.0000896 AC: 3 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.000674 AC: 36 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000182 AC: 202 AN: 1111996

Other (OTH) AF: 0.000232 AC: 14 AN: 60394

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000378 AC: 4 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000162 Hom.: 0

Bravo AF: 0.000121

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000165 AC: 20

EpiCase AF: 0.000327

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.74	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.60
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.047	D
Polyphen		0.99	D
Vest4		0.63
MVP		0.73
MPC		1.8
ClinPred		0.53	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.39
gMVP		0.81
Mutation Taster		=85/15	polymorphism

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: rs202167869; hg19: chr8-26484184;