8-1548914-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001346810.2(DLGAP2):c.461A>C(p.Asp154Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DLGAP2 NM_001346810.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.98

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24601421).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP2	NM_001346810.2	c.461A>C	p.Asp154Ala	missense_variant	5/15	ENST00000637795.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP2	ENST00000637795.2	c.461A>C	p.Asp154Ala	missense_variant	5/15	5	NM_001346810.2
DLGAP2	ENST00000520901.5	c.272A>C	p.Asp91Ala	missense_variant	1/10	1
DLGAP2	ENST00000421627.7	c.458A>C	p.Asp153Ala	missense_variant	5/15	5
DLGAP2	ENST00000612087.1	c.221A>C	p.Asp74Ala	missense_variant	2/11	5		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.221A>C (p.D74A) alteration is located in exon 2 (coding exon 1) of the DLGAP2 gene. This alteration results from a A to C substitution at nucleotide position 221, causing the aspartic acid (D) at amino acid position 74 to be replaced by an alanine (A). 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	0.20
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.036	T;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.57	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.57	T
Polyphen		0.91	.;P;.
Vest4		0.77
MutPred		0.22		.;Gain of glycosylation at S158 (P = 0.1117);.;
MVP		0.13
MPC		0.13
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.25
gMVP		0.54

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: chr8-1497080;