chr2-26924974-C-G

Variant names:

• chr2-26924974-C-G
• NM_020134.4:c.349C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020134.4(DPYSL5):​c.349C>G​(p.Arg117Gly) 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 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DPYSL5 NM_020134.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL5	NM_020134.4	c.349C>G	p.Arg117Gly	missense_variant	Exon 3 of 13	ENST00000288699.11	NP_064519.2
DPYSL5	NM_001253723.2	c.349C>G	p.Arg117Gly	missense_variant	Exon 3 of 13		NP_001240652.1
DPYSL5	NM_001253724.2	c.349C>G	p.Arg117Gly	missense_variant	Exon 3 of 13		NP_001240653.1
DPYSL5	XM_024453007.2	c.349C>G	p.Arg117Gly	missense_variant	Exon 3 of 13		XP_024308775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL5	ENST00000288699.11	c.349C>G	p.Arg117Gly	missense_variant	Exon 3 of 13	1	NM_020134.4	ENSP00000288699.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	.;D;D;T;D;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D;.;.;D;D;D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D;D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Uncertain	2.6	.;M;M;.;M;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.3	D;D;D;D;.;D
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	D;D;D;D;.;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D
Polyphen		1.0	.;D;D;.;D;.
Vest4		0.76, 0.76, 0.76
MutPred		0.63		Gain of ubiquitination at K115 (P = 0.0597);Gain of ubiquitination at K115 (P = 0.0597);Gain of ubiquitination at K115 (P = 0.0597);Gain of ubiquitination at K115 (P = 0.0597);Gain of ubiquitination at K115 (P = 0.0597);Gain of ubiquitination at K115 (P = 0.0597);
MVP		0.84
MPC		2.2
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.92
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-27147842;