rs955980

Variant names:

• chr8-909982-T-G
• rs955980
• NM_001346810.2:c.73+2016T>G

Variant summary

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

The NM_001346810.2(DLGAP2):​c.73+2016T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,280 control chromosomes in the GnomAD database, including 1,494 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 0.12 (1494 hom., cov: 33)
• Consequence: DLGAP2 NM_001346810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP2	NM_001346810.2	c.73+2016T>G		intron_variant	Intron 2 of 14	ENST00000637795.2	NP_001333739.1
DLGAP2	NR_073397.2	n.355+2016T>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP2	ENST00000637795.2	c.73+2016T>G		intron_variant	Intron 2 of 14	5	NM_001346810.2	ENSP00000489774.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18926 AN: 152162 Hom.: 1487 Cov.: 33

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.124 AC: 18945 AN: 152280 Hom.: 1494 Cov.: 33 AF XY: 0.128 AC XY: 9510 AN XY: 74464

African (AFR) AF: 0.0779 AC: 3238 AN: 41562

American (AMR) AF: 0.260 AC: 3974 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3468

East Asian (EAS) AF: 0.173 AC: 896 AN: 5184

South Asian (SAS) AF: 0.145 AC: 699 AN: 4824

European-Finnish (FIN) AF: 0.126 AC: 1342 AN: 10624

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

European-Non Finnish (NFE) AF: 0.121 AC: 8207 AN: 68008

Other (OTH) AF: 0.115 AC: 243 AN: 2116

Alfa AF: 0.116 Hom.: 1384

Bravo AF: 0.134

Asia WGS AF: 0.163 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.36
PhyloP100		-0.35

Splicing

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

Other links and lift over

dbSNP: rs955980; hg19: chr8-859982;