8-26581971-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001197293.3(DPYSL2):c.357C>T(p.Ser119=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,613,358 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (2 hom.)
• Consequence: DPYSL2 NM_001197293.3 splice_region, synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.457

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 8-26581971-C-T is Benign according to our data. Variant chr8-26581971-C-T is described in ClinVar as [Benign]. Clinvar id is 777831.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.457 with no splicing effect.
• BS2: High AC in GnomAd at 158 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPYSL2	NM_001197293.3	c.357C>T	p.Ser119=	splice_region_variant, synonymous_variant	2/14	ENST00000521913.7
DPYSL2	NM_001386.6	c.42C>T	p.Ser14=	splice_region_variant, synonymous_variant	2/14
DPYSL2	NM_001244604.2	c.-67C>T		splice_region_variant, 5_prime_UTR_variant	2/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYSL2	ENST00000521913.7	c.357C>T	p.Ser119=	splice_region_variant, synonymous_variant	2/14	1	NM_001197293.3
DPYSL2	ENST00000311151.9	c.42C>T	p.Ser14=	splice_region_variant, synonymous_variant	2/14	1		P1
DPYSL2	ENST00000493789.6	c.258C>T	p.Ser86=	splice_region_variant, synonymous_variant	2/3	4
DPYSL2	ENST00000523027.1	c.-67C>T		splice_region_variant, 5_prime_UTR_variant	2/14	2

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 158 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00110 AC: 276 AN: 251184 Hom.: 1 AF XY: 0.00110 AC XY: 150 AN XY: 135796

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000279

Gnomad NFE exome AF: 0.00220

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00171 AC: 2498 AN: 1461068 Hom.: 2 Cov.: 30 AF XY: 0.00166 AC XY: 1210 AN XY: 726882

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.000263

Gnomad4 NFE exome AF: 0.00216

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.00104 AC: 158 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.000900 AC XY: 67 AN XY: 74482

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00145 Hom.: 0

Bravo AF: 0.00104

EpiCase AF: 0.00213

EpiControl AF: 0.00160

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	6.0
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs138340807; hg19: chr8-26439487; COSMIC: COSV60785270;