8-26624255-T-G

Variant names:

• chr8-26624255-T-G
• rs327222
• NM_001197293.3:c.741T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001197293.3(DPYSL2):​c.741T>G​(p.Ser247Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: DPYSL2 NM_001197293.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.77
• Publications: 20 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32026836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.741T>G	p.Ser247Arg	missense_variant	Exon 4 of 14	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.426T>G	p.Ser142Arg	missense_variant	Exon 4 of 14		NP_001377.1
DPYSL2	NM_001244604.2	c.318T>G	p.Ser106Arg	missense_variant	Exon 4 of 14		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.741T>G	p.Ser247Arg	missense_variant	Exon 4 of 14	1	NM_001197293.3	ENSP00000427985.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	9.0
DANN	Benign	0.96
DEOGEN2	Uncertain	0.47	.;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.057	N
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.1	.;M;.
PhyloP100		-3.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.9	.;N;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0010	.;D;D
Sift4G	Pathogenic	0.0010	.;D;D
Polyphen		0.028	.;B;.
Vest4		0.41, 0.40
MutPred		0.72		.;Loss of ubiquitination at K146 (P = 0.0672);.;
MVP		0.56
MPC		0.97
ClinPred		0.60	D
GERP RS		-12
Varity_R		0.90
gMVP		0.96
Mutation Taster		=65/35	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: rs327222; hg19: chr8-26481771;