8-1470408-C-T

Variant names:

• chr8-1470408-C-T
• rs4876063
• NM_001346810.2:c.107-30958C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001346810.2(DLGAP2):​c.107-30958C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,908 control chromosomes in the GnomAD database, including 14,212 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 0.43 (14212 hom., cov: 31)
• Consequence: DLGAP2 NM_001346810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972
• Publications: 1 publications found

Genes affected

DLGAP2 (HGNC:2906): (DLG associated protein 2) The product of this gene is a membrane-associated protein that may play a role in synapse organization and signalling in neuronal cells. This gene is biallelically expressed in the brain, however, only the paternal allele is expressed in the testis (PMID:18055845). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jun 2014]

DLGAP2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP2	NM_001346810.2	c.107-30958C>T		intron_variant	Intron 3 of 14	ENST00000637795.2	NP_001333739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP2	ENST00000637795.2	c.107-30958C>T		intron_variant	Intron 3 of 14	5	NM_001346810.2	ENSP00000489774.1
DLGAP2	ENST00000421627.7	c.104-30958C>T		intron_variant	Intron 3 of 14	5		ENSP00000400258.3

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64978 AN: 151788 Hom.: 14202 Cov.: 31

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.457

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.428 AC: 65016 AN: 151908 Hom.: 14212 Cov.: 31 AF XY: 0.423 AC XY: 31387 AN XY: 74228

African (AFR) AF: 0.431 AC: 17868 AN: 41414

American (AMR) AF: 0.390 AC: 5952 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1519 AN: 3468

East Asian (EAS) AF: 0.161 AC: 836 AN: 5184

South Asian (SAS) AF: 0.346 AC: 1665 AN: 4806

European-Finnish (FIN) AF: 0.424 AC: 4471 AN: 10556

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.459 AC: 31183 AN: 67908

Other (OTH) AF: 0.455 AC: 959 AN: 2106

Alfa AF: 0.442 Hom.: 51360

Bravo AF: 0.427

Asia WGS AF: 0.247 AC: 856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.72
DANN	Benign	0.44
PhyloP100		-0.97

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4876063; hg19: chr8-1418574;