14-55151907-A-G

Position:

• chr14-55151907-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014750.5(DLGAP5):​c.2156T>C​(p.Leu719Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DLGAP5 NM_014750.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27358928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP5	NM_014750.5	c.2156T>C	p.Leu719Ser	missense_variant	17/19	ENST00000247191.7	NP_055565.3
DLGAP5	NM_001146015.2	c.2156T>C	p.Leu719Ser	missense_variant	17/20		NP_001139487.1
DLGAP5	XM_017021840.3	c.2156T>C	p.Leu719Ser	missense_variant	17/19		XP_016877329.1
DLGAP5	XM_047432016.1	c.2156T>C	p.Leu719Ser	missense_variant	17/20		XP_047287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP5	ENST00000247191.7	c.2156T>C	p.Leu719Ser	missense_variant	17/19	1	NM_014750.5	ENSP00000247191.2
DLGAP5	ENST00000395425.6	c.2156T>C	p.Leu719Ser	missense_variant	17/20	1		ENSP00000378815.2
DLGAP5	ENST00000554007.1	n.90T>C		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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 07, 2022

The c.2156T>C (p.L719S) alteration is located in exon 17 (coding exon 16) of the DLGAP5 gene. This alteration results from a T to C substitution at nucleotide position 2156, causing the leucine (L) at amino acid position 719 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	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;T
Eigen	Benign	-0.081
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0090	D;T
Polyphen		1.0	.;D
Vest4		0.44
MutPred		0.43		Gain of disorder (P = 0.0083);Gain of disorder (P = 0.0083);
MVP		0.42
MPC		0.44
ClinPred		0.94	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.12
gMVP		0.19

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: chr14-55618625;