rs2301963

Variant names:

• chr8-1565843-C-A
• rs2301963
• NM_001346810.2:c.1391C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001346810.2(DLGAP2):​c.1391C>A​(p.Pro464Gln) variant causes a missense change. The variant allele was found at a frequency of 0.457 in 1,611,828 control chromosomes in the GnomAD database, including 170,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15380 hom., cov: 32)
  • Exomes 𝑓: 0.46 (155190 hom.)
• Consequence: DLGAP2 NM_001346810.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.47
• Publications: 46 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-AS1 (HGNC:50467): (DLGAP2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.1404028E-4).
• BP6: Variant 8-1565843-C-A is Benign according to our data. Variant chr8-1565843-C-A is described in ClinVar as Benign. ClinVar VariationId is 1272088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346810.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP2	NM_001346810.2	MANE Select	c.1391C>A	p.Pro464Gln	missense	Exon 6 of 15	NP_001333739.1	A0A1B0GTN4
	DLGAP2-AS1	NR_103863.1		n.358-105G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP2	ENST00000637795.2	TSL:5 MANE Select	c.1391C>A	p.Pro464Gln	missense	Exon 6 of 15	ENSP00000489774.1	A0A1B0GTN4
	DLGAP2	ENST00000520901.5	TSL:1	c.1199C>A	p.Pro400Gln	missense	Exon 2 of 10	ENSP00000430563.3	H0YBY6
	DLGAP2	ENST00000421627.7	TSL:5	c.1388C>A	p.Pro463Gln	missense	Exon 6 of 15	ENSP00000400258.3	Q9P1A6-1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67870 AN: 151828 Hom.: 15366 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.472

GnomAD2 exomes AF: 0.486 AC: 119394 AN: 245912 AF XY: 0.484

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.638

Gnomad ASJ exome AF: 0.478

Gnomad EAS exome AF: 0.458

Gnomad FIN exome AF: 0.407

Gnomad NFE exome AF: 0.453

Gnomad OTH exome AF: 0.501

GnomAD4 exome AF: 0.458 AC: 668871 AN: 1459882 Hom.: 155190 Cov.: 63 AF XY: 0.461 AC XY: 335016 AN XY: 726108

African (AFR) AF: 0.386 AC: 12902 AN: 33440

American (AMR) AF: 0.634 AC: 28149 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 12627 AN: 26120

East Asian (EAS) AF: 0.478 AC: 18951 AN: 39612

South Asian (SAS) AF: 0.557 AC: 47884 AN: 86042

European-Finnish (FIN) AF: 0.405 AC: 21563 AN: 53268

Middle Eastern (MID) AF: 0.569 AC: 3275 AN: 5756

European-Non Finnish (NFE) AF: 0.446 AC: 495274 AN: 1110926

Other (OTH) AF: 0.468 AC: 28246 AN: 60306

GnomAD4 genome AF: 0.447 AC: 67913 AN: 151946 Hom.: 15380 Cov.: 32 AF XY: 0.451 AC XY: 33458 AN XY: 74232

African (AFR) AF: 0.394 AC: 16312 AN: 41418

American (AMR) AF: 0.558 AC: 8524 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1672 AN: 3470

East Asian (EAS) AF: 0.462 AC: 2375 AN: 5138

South Asian (SAS) AF: 0.553 AC: 2662 AN: 4810

European-Finnish (FIN) AF: 0.402 AC: 4250 AN: 10572

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30506 AN: 67952

Other (OTH) AF: 0.475 AC: 1002 AN: 2110

Alfa AF: 0.455 Hom.: 69407

Bravo AF: 0.459

TwinsUK AF: 0.448 AC: 1660

ALSPAC AF: 0.439 AC: 1691

ESP6500AA AF: 0.373 AC: 1604

ESP6500EA AF: 0.447 AC: 3828

ExAC AF: 0.477 AC: 57738

Asia WGS AF: 0.520 AC: 1808 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.00021	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.5
PrimateAI	Uncertain	0.53	T
REVEL	Benign	0.084
Sift4G	Uncertain	0.040	D
Polyphen		0.92	P
Vest4		0.21
MPC		0.097
ClinPred		0.039	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.40
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2301963; hg19: chr8-1514009; COSMIC: COSV70102130;