18-54591232-C-A

Variant names:

• chr18-54591232-C-A
• rs1413477736
• ENST00000321600.1:c.28C>A

Variant summary

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

The NM_001307955.1(DYNAP):​c.37C>A​(p.Gln13Lys) 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. 15/21 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: DYNAP NM_001307955.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.618

Genes affected

DYNAP (HGNC:26808): (dynactin associated protein) Involved in several processes, including activation of protein kinase B activity; cellular response to ergosterol; and positive regulation of cell population proliferation. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08440742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNAP	NM_001307955.1	c.37C>A	p.Gln13Lys	missense_variant	Exon 2 of 3		NP_001294884.1
DYNAP	XM_011525923.4	c.37C>A	p.Gln13Lys	missense_variant	Exon 3 of 5		XP_011524225.1
DYNAP	XM_017025709.2	c.37C>A	p.Gln13Lys	missense_variant	Exon 3 of 4		XP_016881198.1
DYNAP	NM_173629.3	c.-51C>A		upstream_gene_variant		ENST00000648945.2	NP_775900.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNAP	ENST00000321600.1	c.28C>A	p.Gln10Lys	missense_variant	Exon 1 of 3	2		ENSP00000315265.1
DYNAP	ENST00000585973.1	c.37C>A	p.Gln13Lys	missense_variant	Exon 2 of 3	3		ENSP00000466577.1
DYNAP	ENST00000648945.2	c.-51C>A		upstream_gene_variant			NM_173629.3	ENSP00000496812.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.28C>A (p.Q10K) alteration is located in exon 1 (coding exon 1) of the DYNAP gene. This alteration results from a C to A substitution at nucleotide position 28, causing the glutamine (Q) at amino acid position 10 to be replaced by a lysine (K). 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	0.074
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.30
DANN	Benign	0.29
DEOGEN2	Benign	0.0071	.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.39	.;N
REVEL	Benign	0.023
Sift	Pathogenic	0.0	.;D
Sift4G	Benign	0.33	T;T
Polyphen		0.78	.;P
Vest4		0.18
MutPred		0.19		.;Gain of ubiquitination at Q10 (P = 0.0198);
MVP		0.085
MPC		0.017
ClinPred		0.15	T
GERP RS		-1.8
Varity_R		0.098
gMVP		0.028

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

Other links and lift over

dbSNP: rs1413477736; hg19: chr18-52258463;