chr2-26898617-C-G

Position:

• chr2-26898617-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_020134.4(DPYSL5):​c.118C>G​(p.Arg40Gly) 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPYSL5 NM_020134.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.633

Genes affected

DPYSL5 (HGNC:20637): (dihydropyrimidinase like 5) This gene encodes a member of the CRMP (collapsing response mediator protein) family thought to be involved in neural development. Antibodies to the encoded protein were found in some patients with neurologic symptoms who had paraneoplastic syndrome. A pseudogene of this gene is found on chromosome 11. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DPYSL5. . Gene score misZ 3.0829 (greater than the threshold 3.09). Trascript score misZ 3.7328 (greater than threshold 3.09). GenCC has associacion of gene with Ritscher-Schinzel syndrome 4, syndromic intellectual disability.
• BP4: Computational evidence support a benign effect (MetaRNN=0.20767084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYSL5	NM_020134.4	c.118C>G	p.Arg40Gly	missense_variant	2/13	ENST00000288699.11	NP_064519.2
DPYSL5	NM_001253723.2	c.118C>G	p.Arg40Gly	missense_variant	2/13		NP_001240652.1
DPYSL5	NM_001253724.2	c.118C>G	p.Arg40Gly	missense_variant	2/13		NP_001240653.1
DPYSL5	XM_024453007.2	c.118C>G	p.Arg40Gly	missense_variant	2/13		XP_024308775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL5	ENST00000288699.11	c.118C>G	p.Arg40Gly	missense_variant	2/13	1	NM_020134.4	ENSP00000288699	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

DPYSL5-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 05, 2024

The DPYSL5 c.118C>G variant is predicted to result in the amino acid substitution p.Arg40Gly. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	.;T;T;T;T;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.48	N
LIST_S2	Pathogenic	0.98	D;.;.;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.21	T;T;T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.90	.;L;L;.;L;.
MutationTaster	Benign	0.86	N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.9	D;N;N;D;.;D
REVEL	Uncertain	0.35
Sift	Benign	0.060	T;T;T;T;.;T
Sift4G	Benign	0.27	T;T;T;T;T;T
Polyphen		0.021	.;B;B;.;B;.
Vest4		0.33, 0.33
MutPred		0.44		Gain of catalytic residue at V38 (P = 0.2319);Gain of catalytic residue at V38 (P = 0.2319);Gain of catalytic residue at V38 (P = 0.2319);Gain of catalytic residue at V38 (P = 0.2319);Gain of catalytic residue at V38 (P = 0.2319);Gain of catalytic residue at V38 (P = 0.2319);
MVP		0.24
MPC		1.2
ClinPred		0.92	D
GERP RS		3.7
Varity_R		0.54
gMVP		0.73

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: chr2-27121485;