8-737814-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001346810.2(DLGAP2):c.7G>T(p.Ala3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00993 in 379,658 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (14 hom., cov: 33)
  • Exomes 𝑓: 0.011 (27 hom.)
• Consequence: DLGAP2 NM_001346810.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.27

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]

ERICH1 (HGNC:27234): (glutamate rich 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004456252).
• BP6: Variant 8-737814-G-T is Benign according to our data. Variant chr8-737814-G-T is described in ClinVar as [Benign]. Clinvar id is 3039242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00888 (1345/151410) while in subpopulation SAS AF= 0.0321 (155/4834). AF 95% confidence interval is 0.0279. There are 14 homozygotes in gnomad4. There are 643 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP2	NM_001346810.2	c.7G>T	p.Ala3Ser	missense_variant	1/15	ENST00000637795.2
DLGAP2	NR_073397.2	n.187G>T		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP2	ENST00000637795.2	c.7G>T	p.Ala3Ser	missense_variant	1/15	5	NM_001346810.2

Frequencies

GnomAD3 genomes AF: 0.00888 AC: 1344 AN: 151302 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00636

Gnomad EAS AF: 0.000973

Gnomad SAS AF: 0.0318

Gnomad FIN AF: 0.00496

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0106

GnomAD4 exome AF: 0.0106 AC: 2425 AN: 228248 Hom.: 27 Cov.: 0 AF XY: 0.0110 AC XY: 1277 AN XY: 116330

Gnomad4 AFR exome AF: 0.00316

Gnomad4 AMR exome AF: 0.00737

Gnomad4 ASJ exome AF: 0.00538

Gnomad4 EAS exome AF: 0.0000464

Gnomad4 SAS exome AF: 0.0303

Gnomad4 FIN exome AF: 0.00694

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.0104

GnomAD4 genome AF: 0.00888 AC: 1345 AN: 151410 Hom.: 14 Cov.: 33 AF XY: 0.00869 AC XY: 643 AN XY: 73980

Gnomad4 AFR AF: 0.00207

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00636

Gnomad4 EAS AF: 0.000976

Gnomad4 SAS AF: 0.0321

Gnomad4 FIN AF: 0.00496

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.0105

Alfa AF: 0.00295 Hom.: 0

Bravo AF: 0.00829

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

DLGAP2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	22
Dann	Benign	0.97
DEOGEN2	Benign	0.0068	T
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0045	T
GERP RS		1.7
gMVP		0.021

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs112628444; hg19: chr8-687814;