rs2044853

chr2-38847956-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198963.3(DHX57):c.2164+313T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 151,580 control chromosomes in the GnomAD database, including 65,623 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 0.92 (65623 hom., cov: 27)
• Consequence: DHX57 NM_198963.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.839

Genes affected

DHX57 (HGNC:20086): (DExH-box helicase 57) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

LOC105374470 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHX57	NM_198963.3	c.2164+313T>C		intron_variant		ENST00000457308.6
LOC105374470	XR_001739419.2	n.114+5013A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHX57	ENST00000457308.6	c.2164+313T>C		intron_variant		1	NM_198963.3	P1
DHX57	ENST00000620517.4	c.*462+313T>C		intron_variant, NMD_transcript_variant		1
DHX57	ENST00000622155.4	n.3187+313T>C		intron_variant, non_coding_transcript_variant		1
DHX57	ENST00000452978.5	c.134+313T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.923 AC: 139770 AN: 151462 Hom.: 65577 Cov.: 27

Gnomad AFR AF: 0.730

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.991

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.952

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

GnomAD4 genome AF: 0.923 AC: 139873 AN: 151580 Hom.: 65623 Cov.: 27 AF XY: 0.926 AC XY: 68574 AN XY: 74090

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.975

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.991

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.953

Alfa AF: 0.953 Hom.: 8506

Bravo AF: 0.912

Asia WGS AF: 0.984 AC: 3419 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.1
Dann	Benign	0.20

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: rs2044853; hg19: chr2-39075098; COSMIC: COSV54891797;