rs4129418

Positions:

• chr8-1276836-G-A
• chr8-1276836-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001346810.2(DLGAP2):​c.106+17953G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,020 control chromosomes in the GnomAD database, including 17,111 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 0.47 (17111 hom., cov: 33)
• Consequence: DLGAP2 NM_001346810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP2	NM_001346810.2	c.106+17953G>A		intron_variant		ENST00000637795.2	NP_001333739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP2	ENST00000637795.2	c.106+17953G>A		intron_variant		5	NM_001346810.2	ENSP00000489774
DLGAP2	ENST00000421627.7	c.103+17953G>A		intron_variant		5		ENSP00000400258

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71138 AN: 151902 Hom.: 17100 Cov.: 33

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.468 AC: 71183 AN: 152020 Hom.: 17111 Cov.: 33 AF XY: 0.471 AC XY: 34980 AN XY: 74320

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.504

Alfa AF: 0.485 Hom.: 5746

Bravo AF: 0.470

Asia WGS AF: 0.643 AC: 2238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4129418; hg19: chr8-1226836;