NM_001197293.3:c.1821T>C

Variant names:

• chr8-26653276-T-C
• rs708621
• NM_001197293.3:c.1821T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001197293.3(DPYSL2):​c.1821T>C​(p.Pro607Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,613,874 control chromosomes in the GnomAD database, including 369,024 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 0.68 (36232 hom., cov: 31)
  • Exomes 𝑓: 0.67 (332792 hom.)
• Consequence: DPYSL2 NM_001197293.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.64
• Publications: 24 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-7.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.1821T>C	p.Pro607Pro	synonymous_variant	Exon 13 of 14	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.1506T>C	p.Pro502Pro	synonymous_variant	Exon 13 of 14		NP_001377.1
DPYSL2	NM_001244604.2	c.1398T>C	p.Pro466Pro	synonymous_variant	Exon 13 of 14		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.1821T>C	p.Pro607Pro	synonymous_variant	Exon 13 of 14	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000311151.9	c.1506T>C	p.Pro502Pro	synonymous_variant	Exon 13 of 14	1		ENSP00000309539.5
DPYSL2	ENST00000523027.1	c.1398T>C	p.Pro466Pro	synonymous_variant	Exon 13 of 14	2		ENSP00000431117.1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103369 AN: 151958 Hom.: 36187 Cov.: 31

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.650

GnomAD2 exomes AF: 0.616 AC: 154684 AN: 251242 AF XY: 0.619

Gnomad AFR exome AF: 0.777

Gnomad AMR exome AF: 0.374

Gnomad ASJ exome AF: 0.598

Gnomad EAS exome AF: 0.413

Gnomad FIN exome AF: 0.759

Gnomad NFE exome AF: 0.690

Gnomad OTH exome AF: 0.619

GnomAD4 exome AF: 0.668 AC: 977160 AN: 1461798 Hom.: 332792 Cov.: 59 AF XY: 0.665 AC XY: 483449 AN XY: 727194

African (AFR) AF: 0.773 AC: 25870 AN: 33478

American (AMR) AF: 0.388 AC: 17331 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 15709 AN: 26134

East Asian (EAS) AF: 0.360 AC: 14302 AN: 39696

South Asian (SAS) AF: 0.555 AC: 47876 AN: 86252

European-Finnish (FIN) AF: 0.764 AC: 40787 AN: 53418

Middle Eastern (MID) AF: 0.544 AC: 3137 AN: 5768

European-Non Finnish (NFE) AF: 0.695 AC: 772793 AN: 1111952

Other (OTH) AF: 0.652 AC: 39355 AN: 60386

GnomAD4 genome AF: 0.680 AC: 103459 AN: 152076 Hom.: 36232 Cov.: 31 AF XY: 0.674 AC XY: 50066 AN XY: 74328

African (AFR) AF: 0.772 AC: 32026 AN: 41476

American (AMR) AF: 0.479 AC: 7316 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2124 AN: 3472

East Asian (EAS) AF: 0.407 AC: 2095 AN: 5144

South Asian (SAS) AF: 0.537 AC: 2588 AN: 4820

European-Finnish (FIN) AF: 0.763 AC: 8076 AN: 10590

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47097 AN: 67976

Other (OTH) AF: 0.647 AC: 1367 AN: 2112

Alfa AF: 0.669 Hom.: 117753

Bravo AF: 0.662

Asia WGS AF: 0.473 AC: 1644 AN: 3478

EpiCase AF: 0.669

EpiControl AF: 0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.51
PhyloP100		-7.6
Mutation Taster		=99/1	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: rs708621; hg19: chr8-26510792; COSMIC: COSV60783556;