rs4354330

Positions:

• chr8-1655908-C-T

Variant summary

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

The NM_001346810.2(DLGAP2):​c.1811-12421C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,120 control chromosomes in the GnomAD database, including 10,221 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 0.36 (10221 hom., cov: 34)
• Consequence: DLGAP2 NM_001346810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP2	NM_001346810.2	c.1811-12421C>T		intron_variant		ENST00000637795.2	NP_001333739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP2	ENST00000637795.2	c.1811-12421C>T		intron_variant		5	NM_001346810.2	ENSP00000489774.1
DLGAP2	ENST00000520901.5	c.1619-12421C>T		intron_variant		1		ENSP00000430563.3
DLGAP2	ENST00000421627.7	c.1808-12421C>T		intron_variant		5		ENSP00000400258.3
DLGAP2	ENST00000612087.1	c.1571-12421C>T		intron_variant		5		ENSP00000484215.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55213 AN: 152000 Hom.: 10206 Cov.: 34

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.363 AC: 55275 AN: 152120 Hom.: 10221 Cov.: 34 AF XY: 0.368 AC XY: 27389 AN XY: 74360

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.366

Alfa AF: 0.358 Hom.: 1232

Bravo AF: 0.366

Asia WGS AF: 0.361 AC: 1255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.70
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs4354330; hg19: chr8-1604074;