NM_001197293.3:c.741T>C

Variant names:

• chr8-26624255-T-C
• rs327222
• NM_001197293.3:c.741T>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.741T>C​(p.Ser247Ser) 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
• Publications: 20 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=-0.9).
• 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 rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.741T>C	p.Ser247Ser	synonymous_variant	Exon 4 of 14	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.426T>C	p.Ser142Ser	synonymous_variant	Exon 4 of 14		NP_001377.1
DPYSL2	NM_001244604.2	c.318T>C	p.Ser106Ser	synonymous_variant	Exon 4 of 14		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7	c.741T>C	p.Ser247Ser	synonymous_variant	Exon 4 of 14	1	NM_001197293.3	ENSP00000427985.2

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

GnomAD2 exomes AF: 0.969 AC: 243729 AN: 251470 AF XY: 0.973

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 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

African (AFR) AF: 0.900 AC: 30136 AN: 33480

American (AMR) AF: 0.928 AC: 41515 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 25907 AN: 26136

East Asian (EAS) AF: 0.909 AC: 36100 AN: 39700

South Asian (SAS) AF: 0.980 AC: 84565 AN: 86258

European-Finnish (FIN) AF: 0.998 AC: 53316 AN: 53420

Middle Eastern (MID) AF: 0.989 AC: 5701 AN: 5766

European-Non Finnish (NFE) AF: 0.991 AC: 1101509 AN: 1112004

Other (OTH) AF: 0.979 AC: 59107 AN: 60394

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

African (AFR) AF: 0.902 AC: 37464 AN: 41548

American (AMR) AF: 0.935 AC: 14302 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 3439 AN: 3472

East Asian (EAS) AF: 0.916 AC: 4741 AN: 5174

South Asian (SAS) AF: 0.979 AC: 4724 AN: 4826

European-Finnish (FIN) AF: 0.999 AC: 10611 AN: 10626

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.991 AC: 67416 AN: 68044

Other (OTH) AF: 0.973 AC: 2052 AN: 2110

Alfa AF: 0.981 Hom.: 98474

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
PhyloP100		-3.8
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: rs327222; hg19: chr8-26481771; COSMIC: COSV108133927; COSMIC: COSV108133927;