16-72106654-G-A

Variant names:

• chr16-72106654-G-A
• rs2287997
• NM_014003.4:c.2600+537G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014003.4(DHX38):​c.2600+537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,862 control chromosomes in the GnomAD database, including 2,668 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2668 hom., cov: 32)
• Consequence: DHX38 NM_014003.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 15 publications found

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]

DHX38 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 84

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD, AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014003.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX38	NM_014003.4	MANE Select	c.2600+537G>A		intron	N/A	NP_054722.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX38	ENST00000268482.8	TSL:1 MANE Select	c.2600+537G>A		intron	N/A	ENSP00000268482.3
	DHX38	ENST00000904787.1		c.2678+537G>A		intron	N/A	ENSP00000574846.1
	DHX38	ENST00000904788.1		c.2600+537G>A		intron	N/A	ENSP00000574847.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25945 AN: 151744 Hom.: 2670 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.171 AC: 25939 AN: 151862 Hom.: 2668 Cov.: 32 AF XY: 0.175 AC XY: 12974 AN XY: 74210

African (AFR) AF: 0.0786 AC: 3258 AN: 41432

American (AMR) AF: 0.184 AC: 2799 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 810 AN: 3472

East Asian (EAS) AF: 0.277 AC: 1423 AN: 5144

South Asian (SAS) AF: 0.388 AC: 1867 AN: 4806

European-Finnish (FIN) AF: 0.188 AC: 1981 AN: 10538

Middle Eastern (MID) AF: 0.272 AC: 79 AN: 290

European-Non Finnish (NFE) AF: 0.195 AC: 13228 AN: 67910

Other (OTH) AF: 0.196 AC: 414 AN: 2110

Alfa AF: 0.173 Hom.: 293

Bravo AF: 0.163

Asia WGS AF: 0.293 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.56
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2287997; hg19: chr16-72140553;