chr14-55151934-T-C

Position:

• chr14-55151934-T-C

Variant summary

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

The NM_014750.5(DLGAP5):​c.2129A>G​(p.Asn710Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DLGAP5 NM_014750.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.665

Genes affected

DLGAP5 (HGNC:16864): (DLG associated protein 5) Predicted to enable microtubule binding activity. Predicted to be involved in several processes, including centrosome localization; kinetochore assembly; and mitotic spindle organization. Located in several cellular components, including centrosome; cytosol; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

DLGAP5 (HGNC:):

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=0.10873315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP5	NM_014750.5	c.2129A>G	p.Asn710Ser	missense_variant	17/19	ENST00000247191.7	NP_055565.3
DLGAP5	NM_001146015.2	c.2129A>G	p.Asn710Ser	missense_variant	17/20		NP_001139487.1
DLGAP5	XM_017021840.3	c.2129A>G	p.Asn710Ser	missense_variant	17/19		XP_016877329.1
DLGAP5	XM_047432016.1	c.2129A>G	p.Asn710Ser	missense_variant	17/20		XP_047287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP5	ENST00000247191.7	c.2129A>G	p.Asn710Ser	missense_variant	17/19	1	NM_014750.5	ENSP00000247191.2
DLGAP5	ENST00000395425.6	c.2129A>G	p.Asn710Ser	missense_variant	17/20	1		ENSP00000378815.2
DLGAP5	ENST00000554007.1	n.63A>G		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457606 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724902

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

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

Jul 27, 2024

The c.2129A>G (p.N710S) alteration is located in exon 17 (coding exon 16) of the DLGAP5 gene. This alteration results from a A to G substitution at nucleotide position 2129, causing the asparagine (N) at amino acid position 710 to be replaced by a serine (S). 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	0.072
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.4
DANN	Benign	0.64
DEOGEN2	Benign	0.074	.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.036
Sift	Benign	0.042	D;T
Sift4G	Benign	0.093	T;T
Polyphen		0.051	.;B
Vest4		0.15
MutPred		0.31		Gain of disorder (P = 0.0628);Gain of disorder (P = 0.0628);
MVP		0.22
MPC		0.066
ClinPred		0.039	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.065
gMVP		0.052

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: chr14-55618652;