NM_001197293.3:c.*1916C>T

Variant names:

• chr8-26657622-C-T
• rs45471201
• NM_001197293.3:c.*1916C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001197293.3(DPYSL2):​c.*1916C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 152,460 control chromosomes in the GnomAD database, including 624 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 0.088 (618 hom., cov: 33)
  • Exomes 𝑓: 0.14 (6 hom.)
• Consequence: DPYSL2 NM_001197293.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.*1916C>T		3_prime_UTR_variant	Exon 14 of 14	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.*1916C>T		3_prime_UTR_variant	Exon 14 of 14		NP_001377.1
DPYSL2	NM_001244604.2	c.*1916C>T		3_prime_UTR_variant	Exon 14 of 14		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.*1916C>T		3_prime_UTR_variant	Exon 14 of 14	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000311151.9	c.*1916C>T		3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000309539.5

Frequencies

GnomAD3 genomes AF: 0.0883 AC: 13409 AN: 151912 Hom.: 618 Cov.: 33

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0758

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0972

Gnomad OTH AF: 0.0742

GnomAD4 exome AF: 0.137 AC: 59 AN: 430 Hom.: 6 Cov.: 0 AF XY: 0.150 AC XY: 39 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.134 AC: 57 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0882 AC: 13411 AN: 152030 Hom.: 618 Cov.: 33 AF XY: 0.0888 AC XY: 6596 AN XY: 74306

African (AFR) AF: 0.0726 AC: 3010 AN: 41480

American (AMR) AF: 0.0560 AC: 856 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3470

East Asian (EAS) AF: 0.134 AC: 692 AN: 5176

South Asian (SAS) AF: 0.0759 AC: 366 AN: 4824

European-Finnish (FIN) AF: 0.125 AC: 1314 AN: 10514

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0972 AC: 6605 AN: 67966

Other (OTH) AF: 0.0739 AC: 156 AN: 2110

Alfa AF: 0.0908 Hom.: 211

Bravo AF: 0.0830

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs45471201; hg19: chr8-26515138;