rs199869101

Variant names:

• chr8-26643481-C-G
• rs199869101
• NM_001197293.3:c.1169C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-26643481-C-G
• chr8-26643481-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001197293.3(DPYSL2):​c.1169C>G​(p.Thr390Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPYSL2 NM_001197293.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.90

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.1169C>G	p.Thr390Arg	missense_variant	Exon 9 of 14	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.854C>G	p.Thr285Arg	missense_variant	Exon 9 of 14		NP_001377.1
DPYSL2	NM_001244604.2	c.746C>G	p.Thr249Arg	missense_variant	Exon 9 of 14		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.1169C>G	p.Thr390Arg	missense_variant	Exon 9 of 14	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000311151.9	c.854C>G	p.Thr285Arg	missense_variant	Exon 9 of 14	1		ENSP00000309539.5
DPYSL2	ENST00000523027.1	c.746C>G	p.Thr249Arg	missense_variant	Exon 9 of 14	2		ENSP00000431117.1
DPYSL2	ENST00000474808.1	n.525C>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	.;D;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.96	D;D;D
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Uncertain	2.5	.;M;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-4.7	.;D;D
REVEL	Pathogenic	0.87
Sift	Benign	0.072	.;T;T
Sift4G	Benign	0.13	.;T;T
Polyphen		1.0	.;D;.
Vest4		0.92, 0.93
MutPred		0.86		.;Gain of MoRF binding (P = 0.0155);.;
MVP		0.98
MPC		2.1
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.95
gMVP		0.99

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

Publications

LitVar

Other links and lift over

dbSNP: rs199869101; hg19: chr8-26500997;