18-54591224-G-A

Variant names:

• chr18-54591224-G-A
• rs1911059649
• ENST00000321600.1:c.20G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001307955.1(DYNAP):​c.29G>A​(p.Gly10Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,660 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: DYNAP NM_001307955.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0750

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053923905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNAP	NM_001307955.1	c.29G>A	p.Gly10Asp	missense_variant	Exon 2 of 3		NP_001294884.1
DYNAP	XM_011525923.4	c.29G>A	p.Gly10Asp	missense_variant	Exon 3 of 5		XP_011524225.1
DYNAP	XM_017025709.2	c.29G>A	p.Gly10Asp	missense_variant	Exon 3 of 4		XP_016881198.1
DYNAP	NM_173629.3	c.-59G>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.20G>A	p.Gly7Asp	missense_variant	Exon 1 of 3	2		ENSP00000315265.1
DYNAP	ENST00000585973.1	c.29G>A	p.Gly10Asp	missense_variant	Exon 2 of 3	3		ENSP00000466577.1
DYNAP	ENST00000648945.2	c.-59G>A		upstream_gene_variant			NM_173629.3	ENSP00000496812.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459660 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 726078

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: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.20G>A (p.G7D) alteration is located in exon 1 (coding exon 1) of the DYNAP gene. This alteration results from a G to A substitution at nucleotide position 20, causing the glycine (G) at amino acid position 7 to be replaced by an aspartic acid (D). 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	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	1.3
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	.;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.96	.;N
REVEL	Benign	0.053
Sift	Benign	0.051	.;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.090	.;B
Vest4		0.34
MutPred		0.15		.;Gain of helix (P = 0.0199);
MVP		0.17
MPC		0.11
ClinPred		0.081	T
GERP RS		0.13
Varity_R		0.059
gMVP		0.022

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: rs1911059649; hg19: chr18-52258455;