Genetic Variant DYNAP:p.Thr100Arg (chr18-54597889-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_173629.3(DYNAP):c.299C>G(p.Thr100Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,446 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

DYNAP
NM_173629.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNAP	NM_173629.3 link	c.299C>G	p.Thr100Arg	missense_variant	Exon 3 of 3	ENST00000648945.2	NP_775900.2	Q8N1N2
DYNAP	NM_001307955.1 link	c.221C>G	p.Thr74Arg	missense_variant	Exon 3 of 3		NP_001294884.1	K7EMN5
DYNAP	XM_011525923.4 link	c.386C>G	p.Thr129Arg	missense_variant	Exon 5 of 5		XP_011524225.1
DYNAP	XM_017025709.2 link	c.221C>G	p.Thr74Arg	missense_variant	Exon 4 of 4		XP_016881198.1	K7EMN5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DYNAP	ENST00000648945.2 link	c.299C>G	p.Thr100Arg	missense_variant	Exon 3 of 3		NM_173629.3	ENSP00000496812.1	A0A3B3IRJ4
DYNAP	ENST00000321600.1 link	c.377C>G	p.Thr126Arg	missense_variant	Exon 3 of 3	2		ENSP00000315265.1	Q8N1N2
DYNAP	ENST00000585973.1 link	c.221C>G	p.Thr74Arg	missense_variant	Exon 3 of 3	3		ENSP00000466577.1	K7EMN5

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250734

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135496

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461380

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000416

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

Dec 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.377C>G (p.T126R) alteration is located in exon 3 (coding exon 3) of the DYNAP gene. This alteration results from a C to G substitution at nucleotide position 377, causing the threonine (T) at amino acid position 126 to be replaced by an arginine (R). 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

Pathogenic

0.78

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

.;.;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.73

D;D;D

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.0

.;.;M

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-5.7

.;.;D

REVEL

Uncertain

0.29

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0

D;.;D

Polyphen

1.0

.;.;D

Vest4

0.59

MVP

0.24

MPC

0.10

ClinPred

0.97

GERP RS

4.8

Varity_R

0.97

gMVP

0.61

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