Genetic Variant DYNAP:p.Asp2Glu (chr18-54591288-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173629.3(DYNAP):c.6C>G(p.Asp2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,676 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: 0.0000014 ( 0 hom. )

Consequence

DYNAP
NM_173629.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.436

Variant links:

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]

DYNAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.12667656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNAP	NM_173629.3 link	c.6C>G	p.Asp2Glu	missense_variant	Exon 1 of 3	ENST00000648945.2	NP_775900.2	Q8N1N2
DYNAP	NM_001307955.1 link	c.93C>G	p.Asp31Glu	missense_variant	Exon 2 of 3		NP_001294884.1	K7EMN5
DYNAP	XM_011525923.4 link	c.93C>G	p.Asp31Glu	missense_variant	Exon 3 of 5		XP_011524225.1
DYNAP	XM_017025709.2 link	c.93C>G	p.Asp31Glu	missense_variant	Exon 3 of 4		XP_016881198.1	K7EMN5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DYNAP	ENST00000648945.2 link	c.6C>G	p.Asp2Glu	missense_variant	Exon 1 of 3		NM_173629.3	ENSP00000496812.1	A0A3B3IRJ4
DYNAP	ENST00000321600.1 link	c.84C>G	p.Asp28Glu	missense_variant	Exon 1 of 3	2		ENSP00000315265.1	Q8N1N2
DYNAP	ENST00000585973.1 link	c.93C>G	p.Asp31Glu	missense_variant	Exon 2 of 3	3		ENSP00000466577.1	K7EMN5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250598

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135430

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460676

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726634

show subpopulations

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.84C>G (p.D28E) alteration is located in exon 1 (coding exon 1) of the DYNAP gene. This alteration results from a C to G substitution at nucleotide position 84, causing the aspartic acid (D) at amino acid position 28 to be replaced by a glutamic acid (E). 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

0.23

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.022

.;.;T

Eigen

Benign

-0.079

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.37

T;T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

.;.;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.8

.;.;N

REVEL

Benign

0.098

Sift

Benign

0.17

.;.;T

Sift4G

Benign

0.35

T;.;T

Polyphen

0.99

.;.;D

Vest4

0.20

MutPred

0.29

.;.;Gain of helix (P = 0.0425);

MVP

0.14

MPC

0.015

ClinPred

0.17

GERP RS

0.67

Varity_R

0.051

gMVP

0.025

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over