16-72096219-AGGTTGGT-A

Variant names:

• chr16-72096219-AGGTTGGT-A
• NM_014003.4:c.66_72delTGGTGGT

Variant summary

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

The NM_014003.4(DHX38):​c.66_72delTGGTGGT​(p.Gly23LeufsTer33) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHX38 NM_014003.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.94

Genes affected

DHX38 (HGNC:17211): (DEAH-box helicase 38) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The protein encoded by this gene is a member of the DEAD/H box family of splicing factors. This protein resembles yeast Prp16 more closely than other DEAD/H family members. It is an ATPase and essential for the catalytic step II in pre-mRNA splicing process. [provided by RefSeq, Jul 2008]

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
DHX38	NM_014003.4	c.66_72delTGGTGGT	p.Gly23LeufsTer33	frameshift_variant	Exon 2 of 27	ENST00000268482.8	NP_054722.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHX38	ENST00000268482.8	c.66_72delTGGTGGT	p.Gly23LeufsTer33	frameshift_variant	Exon 2 of 27	1	NM_014003.4	ENSP00000268482.3
DHX38	ENST00000566794.5	c.66_72delTGGTGGT	p.Gly23LeufsTer33	frameshift_variant	Exon 2 of 3	4		ENSP00000455939.1
DHX38	ENST00000566489.1	c.66_72delTGGTGGT	p.Gly23LeufsTer33	frameshift_variant	Exon 3 of 4	4		ENSP00000457887.1
DHX38	ENST00000579387.5	n.66_72delTGGTGGT		non_coding_transcript_exon_variant	Exon 2 of 12	5		ENSP00000462149.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 24, 2022

This sequence change creates a premature translational stop signal (p.Gly23Leufs*33) in the DHX38 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in DHX38 cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DHX38-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-72130118;