chr16-70350568-G-T

Position:

• chr16-70350568-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018332.5(DDX19A):​c.69G>T​(p.Leu23Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX19A NM_018332.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27

Genes affected

DDX19A (HGNC:25628): (DEAD-box helicase 19A) Predicted to enable RNA binding activity and RNA helicase activity. Predicted to be involved in poly(A)+ mRNA export from nucleus. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29338306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX19A	NM_018332.5	c.69G>T	p.Leu23Phe	missense_variant	2/12	ENST00000302243.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX19A	ENST00000302243.12	c.69G>T	p.Leu23Phe	missense_variant	2/12	1	NM_018332.5	P1
	ENST00000650629.1	n.681-971C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2023

The c.69G>T (p.L23F) alteration is located in exon 2 (coding exon 2) of the DDX19A gene. This alteration results from a G to T substitution at nucleotide position 69, causing the leucine (L) at amino acid position 23 to be replaced by a phenylalanine (F). 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	0.17
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T;.
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	D;D
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.15
Sift	Uncertain	0.020	D;D
Sift4G	Benign	0.078	T;T
Polyphen		0.99	D;.
Vest4		0.53
MutPred		0.14		Loss of ubiquitination at K26 (P = 0.1375);Loss of ubiquitination at K26 (P = 0.1375);
MVP		0.25
MPC		1.6
ClinPred		0.84	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.41

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: rs139832768; hg19: chr16-70384471;