rs327222

chr8-26624255-T-Cchr8-26624255-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001197293.3(DPYSL2):c.741T>C(p.Ser247=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.981 in 1,614,186 control chromosomes in the GnomAD database, including 777,619 homozygotes. 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: 𝑓 0.96 (70081 hom., cov: 33)
  • Exomes 𝑓: 0.98 (707538 hom.)
• Consequence: DPYSL2 NM_001197293.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.77

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-3.77 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPYSL2	NM_001197293.3	c.741T>C	p.Ser247=	synonymous_variant	4/14	ENST00000521913.7
DPYSL2	NM_001386.6	c.426T>C	p.Ser142=	synonymous_variant	4/14
DPYSL2	NM_001244604.2	c.318T>C	p.Ser106=	synonymous_variant	4/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYSL2	ENST00000521913.7	c.741T>C	p.Ser247=	synonymous_variant	4/14	1	NM_001197293.3
DPYSL2	ENST00000311151.9	c.426T>C	p.Ser142=	synonymous_variant	4/14	1		P1
DPYSL2	ENST00000523027.1	c.318T>C	p.Ser106=	synonymous_variant	4/14	2
DPYSL2	ENST00000523093.5	n.407T>C		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes AF: 0.958 AC: 145830 AN: 152186 Hom.: 70028 Cov.: 33

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.993

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.990

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.973

GnomAD3 exomes AF: 0.969 AC: 243729 AN: 251470 Hom.: 118303 AF XY: 0.973 AC XY: 132266 AN XY: 135906

Gnomad AFR exome AF: 0.899

Gnomad AMR exome AF: 0.926

Gnomad ASJ exome AF: 0.991

Gnomad EAS exome AF: 0.907

Gnomad SAS exome AF: 0.980

Gnomad FIN exome AF: 0.998

Gnomad NFE exome AF: 0.992

Gnomad OTH exome AF: 0.976

GnomAD4 exome AF: 0.984 AC: 1437856 AN: 1461882 Hom.: 707538 Cov.: 59 AF XY: 0.984 AC XY: 715680 AN XY: 727248

Gnomad4 AFR exome AF: 0.900

Gnomad4 AMR exome AF: 0.928

Gnomad4 ASJ exome AF: 0.991

Gnomad4 EAS exome AF: 0.909

Gnomad4 SAS exome AF: 0.980

Gnomad4 FIN exome AF: 0.998

Gnomad4 NFE exome AF: 0.991

Gnomad4 OTH exome AF: 0.979

GnomAD4 genome AF: 0.958 AC: 145941 AN: 152304 Hom.: 70081 Cov.: 33 AF XY: 0.958 AC XY: 71379 AN XY: 74482

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.935

Gnomad4 ASJ AF: 0.990

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.979

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.973

Alfa AF: 0.982 Hom.: 86705

Bravo AF: 0.950

Asia WGS AF: 0.938 AC: 3261 AN: 3478

EpiCase AF: 0.991

EpiControl AF: 0.992

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.2
Dann	Benign	0.48

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: rs327222; hg19: chr8-26481771;