18-54591232-C-T

Variant names:

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

Variant summary

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

The NM_001307955.1(DYNAP):​c.37C>T​(p.Gln13*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,652 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: DYNAP NM_001307955.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• 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 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_001307955.1	c.37C>T	p.Gln13*	stop_gained	Exon 2 of 3		NP_001294884.1
DYNAP	XM_011525923.4	c.37C>T	p.Gln13*	stop_gained	Exon 3 of 5		XP_011524225.1
DYNAP	XM_017025709.2	c.37C>T	p.Gln13*	stop_gained	Exon 3 of 4		XP_016881198.1
DYNAP	NM_173629.3	c.-51C>T		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>T	p.Gln10*	stop_gained	Exon 1 of 3	2		ENSP00000315265.1
DYNAP	ENST00000585973.1	c.37C>T	p.Gln13*	stop_gained	Exon 2 of 3	3		ENSP00000466577.1
DYNAP	ENST00000648945.2	c.-51C>T		upstream_gene_variant			NM_173629.3	ENSP00000496812.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249768 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 135008

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459652 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 726076

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	0.36
DANN	Uncertain	0.99
Eigen	Benign	0.040
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.0083	N
Vest4		0.25
GERP RS		-1.8

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;