chr8-26581971-C-T

Variant names:

• chr8-26581971-C-T
• rs138340807
• NM_001197293.3:c.357C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001197293.3(DPYSL2):​c.357C>T​(p.Ser119Ser) 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
• Publications: 8 publications found

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]

DPYSL2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 Homozygotes in GnomAdExome4 at 2 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.357C>T	p.Ser119Ser	splice_region_variant, synonymous_variant	Exon 2 of 14	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001244604.2	c.-67C>T		splice_region_variant	Exon 2 of 14		NP_001231533.1
DPYSL2	NM_001386.6	c.42C>T	p.Ser14Ser	splice_region_variant, synonymous_variant	Exon 2 of 14		NP_001377.1
DPYSL2	NM_001244604.2	c.-67C>T		5_prime_UTR_variant	Exon 2 of 14		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.357C>T	p.Ser119Ser	splice_region_variant, synonymous_variant	Exon 2 of 14	1	NM_001197293.3	ENSP00000427985.2

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

GnomAD2 exomes AF: 0.00110 AC: 276 AN: 251184 AF XY: 0.00110

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 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

African (AFR) AF: 0.000239 AC: 8 AN: 33472

American (AMR) AF: 0.000179 AC: 8 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86242

European-Finnish (FIN) AF: 0.000263 AC: 14 AN: 53218

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00216 AC: 2397 AN: 1111478

Other (OTH) AF: 0.00111 AC: 67 AN: 60372

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

African (AFR) AF: 0.000313 AC: 13 AN: 41560

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00193 AC: 131 AN: 68018

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

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

Jul 07, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.0
DANN	Benign	0.77
PhyloP100		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs138340807; hg19: chr8-26439487; COSMIC: COSV60785270;