chr8-1548974-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001346810.2(DLGAP2):ā€‹c.521A>Gā€‹(p.Asp174Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

DLGAP2
NM_001346810.2 missense

Scores

1
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.59
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DLGAP2NM_001346810.2 linkuse as main transcriptc.521A>G p.Asp174Gly missense_variant 5/15 ENST00000637795.2 NP_001333739.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DLGAP2ENST00000637795.2 linkuse as main transcriptc.521A>G p.Asp174Gly missense_variant 5/155 NM_001346810.2 ENSP00000489774
DLGAP2ENST00000520901.5 linkuse as main transcriptc.332A>G p.Asp111Gly missense_variant 1/101 ENSP00000430563
DLGAP2ENST00000421627.7 linkuse as main transcriptc.518A>G p.Asp173Gly missense_variant 5/155 ENSP00000400258 Q9P1A6-1
DLGAP2ENST00000612087.1 linkuse as main transcriptc.281A>G p.Asp94Gly missense_variant 2/115 ENSP00000484215 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1446832
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
720292
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 28, 2023The c.281A>G (p.D94G) alteration is located in exon 2 (coding exon 1) of the DLGAP2 gene. This alteration results from a A to G substitution at nucleotide position 281, causing the aspartic acid (D) at amino acid position 94 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T;T;T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.47
T;T;T
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
1.5
.;L;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.61
T
REVEL
Uncertain
0.31
Sift4G
Benign
0.20
.;.;T
Polyphen
0.98
.;D;.
Vest4
0.84
MutPred
0.45
.;Gain of catalytic residue at D173 (P = 0.0068);.;
MVP
0.22
MPC
0.16
ClinPred
0.98
D
GERP RS
5.4
Varity_R
0.27
gMVP
0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-1497140; API