rs6558451

Variant names:

• chr8-1341895-G-A
• rs6558451
• NM_001346810.2:c.106+83012G>A

Variant summary

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

The NM_001346810.2(DLGAP2):​c.106+83012G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,086 control chromosomes in the GnomAD database, including 17,803 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 0.44 (17803 hom., cov: 33)
• Consequence: DLGAP2 NM_001346810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• 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

LOC124901869 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP2	NM_001346810.2	c.106+83012G>A		intron_variant	Intron 3 of 14	ENST00000637795.2	NP_001333739.1
LOC124901869	XR_007060782.1	n.5794+14672G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP2	ENST00000637795.2	c.106+83012G>A		intron_variant	Intron 3 of 14	5	NM_001346810.2	ENSP00000489774.1
DLGAP2	ENST00000421627.7	c.103+83012G>A		intron_variant	Intron 3 of 14	5		ENSP00000400258.3

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66698 AN: 151970 Hom.: 17778 Cov.: 33

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.439 AC: 66760 AN: 152086 Hom.: 17803 Cov.: 33 AF XY: 0.430 AC XY: 31959 AN XY: 74356

African (AFR) AF: 0.756 AC: 31351 AN: 41466

American (AMR) AF: 0.298 AC: 4554 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3472

East Asian (EAS) AF: 0.250 AC: 1294 AN: 5178

South Asian (SAS) AF: 0.247 AC: 1189 AN: 4818

European-Finnish (FIN) AF: 0.296 AC: 3129 AN: 10570

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23227 AN: 67980

Other (OTH) AF: 0.431 AC: 910 AN: 2112

Alfa AF: 0.429 Hom.: 3545

Bravo AF: 0.450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.51
PhyloP100		-0.41

Splicing

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

Other links and lift over

dbSNP: rs6558451; hg19: chr8-1290061;