rs11662259

Variant names:

• chr18-3582274-A-C
• rs11662259
• NM_004746.4:c.1592-26T>G

Your query was ambiguous. Multiple possible variants found:

• chr18-3582274-A-C
• chr18-3582274-A-G

Variant summary

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

The NM_001398525.1(DLGAP1):​c.1622-26T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,591,570 control chromosomes in the GnomAD database, including 29,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.18 (2526 hom., cov: 31)
  • Exomes 𝑓: 0.19 (26750 hom.)
• Consequence: DLGAP1 NM_001398525.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776
• Publications: 6 publications found

Genes affected

DLGAP1 (HGNC:2905): (DLG associated protein 1) Predicted to enable molecular adaptor activity. Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in several processes, including aggresome assembly; regulation of postsynaptic neurotransmitter receptor activity; and regulation of proteasomal protein catabolic process. Predicted to be located in plasma membrane. Predicted to be part of postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001398525.1. 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
	DLGAP1	NM_004746.4	MANE Select	c.1592-26T>G		intron	N/A	NP_004737.2
	DLGAP1	NM_001398525.1		c.1622-26T>G		intron	N/A	NP_001385454.1
	DLGAP1	NM_001398526.1		c.1622-26T>G		intron	N/A	NP_001385455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.1592-26T>G		intron	N/A	ENSP00000316377.3
	DLGAP1	ENST00000400147.6	TSL:1	c.686-26T>G		intron	N/A	ENSP00000383011.2
	DLGAP1	ENST00000400145.6	TSL:1	c.686-26T>G		intron	N/A	ENSP00000383010.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27445 AN: 151812 Hom.: 2523 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.201

GnomAD2 exomes AF: 0.195 AC: 46947 AN: 240832 AF XY: 0.200

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.226

Gnomad EAS exome AF: 0.186

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.190 AC: 274168 AN: 1439640 Hom.: 26750 Cov.: 34 AF XY: 0.193 AC XY: 137926 AN XY: 713680

African (AFR) AF: 0.172 AC: 5609 AN: 32596

American (AMR) AF: 0.200 AC: 8403 AN: 42058

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 5629 AN: 25234

East Asian (EAS) AF: 0.151 AC: 5935 AN: 39322

South Asian (SAS) AF: 0.264 AC: 22549 AN: 85540

European-Finnish (FIN) AF: 0.156 AC: 7879 AN: 50614

Middle Eastern (MID) AF: 0.275 AC: 1553 AN: 5640

European-Non Finnish (NFE) AF: 0.187 AC: 205056 AN: 1099288

Other (OTH) AF: 0.195 AC: 11555 AN: 59348

GnomAD4 genome AF: 0.181 AC: 27486 AN: 151930 Hom.: 2526 Cov.: 31 AF XY: 0.181 AC XY: 13445 AN XY: 74248

African (AFR) AF: 0.168 AC: 6974 AN: 41436

American (AMR) AF: 0.183 AC: 2791 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3468

East Asian (EAS) AF: 0.175 AC: 905 AN: 5158

South Asian (SAS) AF: 0.257 AC: 1234 AN: 4810

European-Finnish (FIN) AF: 0.160 AC: 1689 AN: 10548

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12572 AN: 67934

Other (OTH) AF: 0.201 AC: 423 AN: 2104

Alfa AF: 0.189 Hom.: 3565

Bravo AF: 0.185

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	22
DANN	Benign	0.40
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11662259; hg19: chr18-3582272; COSMIC: COSV59807571; COSMIC: COSV59807571;