chr15-51448859-G-A

Position:

• chr15-51448859-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378457.1(DMXL2):​c.*125C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 947,240 control chromosomes in the GnomAD database, including 15,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2136 hom., cov: 32)
  • Exomes 𝑓: 0.18 (13356 hom.)
• Consequence: DMXL2 NM_001378457.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0410

Genes affected

DMXL2 (HGNC:2938): (Dmx like 2) This gene encodes a protein with 12 WD domains. Proteins with WD domains are involved in many functions including participation in signal transduction pathways. Participation of the encoded protein in regulation of the Notch signaling pathway has been demonstrated in vitro using several human cell lines (PMID:20810660). A gene encoding a similar protein is located on chromosome 5. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

DMXL2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-51448859-G-A is Benign according to our data. Variant chr15-51448859-G-A is described in ClinVar as [Benign]. Clinvar id is 1279906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMXL2	NM_001378457.1	c.*125C>T		3_prime_UTR_variant	44/44	ENST00000560891.6	NP_001365386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMXL2	ENST00000560891	c.*125C>T		3_prime_UTR_variant	44/44	1	NM_001378457.1	ENSP00000453267.2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23740 AN: 152006 Hom.: 2138 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0847

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.175 AC: 139149 AN: 795116 Hom.: 13356 Cov.: 11 AF XY: 0.175 AC XY: 71214 AN XY: 406738

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.00697

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.0922

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.156 AC: 23733 AN: 152124 Hom.: 2136 Cov.: 32 AF XY: 0.152 AC XY: 11268 AN XY: 74366

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.0847

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.178

Alfa AF: 0.179 Hom.: 2740

Bravo AF: 0.157

Asia WGS AF: 0.0710 AC: 250 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.68

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: rs3751585; hg19: chr15-51741056;