Variant chr8-1548812-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001346810.2(DLGAP2):c.359A>T(p.Tyr120Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,428,886 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DLGAP2
NM_001346810.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

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]

DLGAP2 links:

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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
DLGAP2	NM_001346810.2 linkuse as main transcript	c.359A>T	p.Tyr120Phe	missense_variant	5/15	ENST00000637795.2	NP_001333739.1	A0A1B0GTN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DLGAP2	ENST00000637795.2 linkuse as main transcript	c.359A>T	p.Tyr120Phe	missense_variant	5/15	5	NM_001346810.2	ENSP00000489774.1	A0A1B0GTN4
DLGAP2	ENST00000520901.5 linkuse as main transcript	c.167A>T	p.Tyr56Phe	missense_variant	1/10	1		ENSP00000430563.3	H0YBY6
DLGAP2	ENST00000421627.7 linkuse as main transcript	c.356A>T	p.Tyr119Phe	missense_variant	5/15	5		ENSP00000400258.3	Q9P1A6-1
DLGAP2	ENST00000612087.1 linkuse as main transcript	c.119A>T	p.Tyr40Phe	missense_variant	2/11	5		ENSP00000484215.1	A0A1B0GXK6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000504

AC:

AN:

198506

Hom.:

AF XY:

0.00

AC XY:

AN XY:

110526

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000317

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1428886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708498

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000469

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.119A>T (p.Y40F) alteration is located in exon 2 (coding exon 1) of the DLGAP2 gene. This alteration results from a A to T substitution at nucleotide position 119, causing the tyrosine (Y) at amino acid position 40 to be replaced by a phenylalanine (F). 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

-0.16

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L;.

PrimateAI

Uncertain

0.75

REVEL

Benign

0.18

Sift4G

Benign

0.088

.;.;T

Polyphen

0.92

.;P;.

Vest4

0.58

MutPred

0.42

.;Loss of phosphorylation at Y119 (P = 0.017);.;

MVP

0.28

MPC

0.12

ClinPred

0.95

GERP RS

4.9

Varity_R

0.11

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over