8-26634815-C-G

Variant names:

• chr8-26634815-C-G
• NM_001197293.3:c.1041C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001197293.3(DPYSL2):​c.1041C>G​(p.Ile347Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DPYSL2 NM_001197293.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.18

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.1041C>G	p.Ile347Met	missense_variant	Exon 8 of 14	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.726C>G	p.Ile242Met	missense_variant	Exon 8 of 14		NP_001377.1
DPYSL2	NM_001244604.2	c.618C>G	p.Ile206Met	missense_variant	Exon 8 of 14		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.1041C>G	p.Ile347Met	missense_variant	Exon 8 of 14	1	NM_001197293.3	ENSP00000427985.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	.;D;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.077	N
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Uncertain	0.36	D
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.5	.;N;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.019	.;D;D
Sift4G	Uncertain	0.017	.;D;D
Polyphen		0.61	.;P;.
Vest4		0.65, 0.64
MutPred		0.66		.;Gain of MoRF binding (P = 0.1045);.;
MVP		0.76
MPC		1.2
ClinPred		0.86	D
GERP RS		-4.8
Varity_R		0.78
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-26492331;