Genetic Variant DYNAP:p.Ile21Val (chr18-54594942-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173629.3(DYNAP):c.61A>G(p.Ile21Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,609,698 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: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

DYNAP
NM_173629.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.340

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 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=0.02094677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNAP	NM_173629.3 link	c.61A>G	p.Ile21Val	missense_variant	Exon 2 of 3	ENST00000648945.2	NP_775900.2	Q8N1N2
DYNAP	XM_011525923.4 link	c.148A>G	p.Ile50Val	missense_variant	Exon 4 of 5		XP_011524225.1
DYNAP	NM_001307955.1 link	c.145-2871A>G		intron_variant	Intron 2 of 2		NP_001294884.1	K7EMN5
DYNAP	XM_017025709.2 link	c.145-2871A>G		intron_variant	Intron 3 of 3		XP_016881198.1	K7EMN5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DYNAP	ENST00000648945.2 link	c.61A>G	p.Ile21Val	missense_variant	Exon 2 of 3		NM_173629.3	ENSP00000496812.1	A0A3B3IRJ4
DYNAP	ENST00000321600.1 link	c.139A>G	p.Ile47Val	missense_variant	Exon 2 of 3	2		ENSP00000315265.1	Q8N1N2
DYNAP	ENST00000585973.1 link	c.145-2871A>G		intron_variant	Intron 2 of 2	3		ENSP00000466577.1	K7EMN5

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000471

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000218

AC:

AN:

247694

Hom.:

AF XY:

0.000217

AC XY:

AN XY:

133872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000593

Gnomad ASJ exome

AF:

0.00121

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000932

Gnomad NFE exome

AF:

0.000329

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000300

AC:

437

AN:

1457648

Hom.:

Cov.:

AF XY:

0.000291

AC XY:

211

AN XY:

725060

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00162

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.000326

Gnomad4 OTH exome

AF:

0.000399

GnomAD4 genome

AF:

0.000296

AC:

AN:

152050

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000344

Hom.:

Bravo

AF:

0.000287

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.000332

EpiControl

AF:

0.000181

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.139A>G (p.I47V) alteration is located in exon 2 (coding exon 2) of the DYNAP gene. This alteration results from a A to G substitution at nucleotide position 139, causing the isoleucine (I) at amino acid position 47 to be replaced by a valine (V). 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

0.073

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.065

DANN

Benign

0.26

DEOGEN2

Benign

0.0050

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.28

T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;L

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.21

.;N

REVEL

Benign

0.10

Sift

Benign

0.28

.;T

Sift4G

Benign

0.75

.;T

Polyphen

0.0010

.;B

Vest4

0.17

MVP

0.014

MPC

0.014

ClinPred

0.073

GERP RS

-2.7

Varity_R

0.022

gMVP

0.012

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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