15-51481264-AACTTCCATTGCCATC-AACTTCCATTGCCATCACTTCCATTGCCATC

Variant names:

• chr15-51481264-A-AACTTCCATTGCCATC
• rs606231461
• NM_001378457.1:c.5827_5841dupGATGGCAATGGAAGT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001378457.1(DMXL2):​c.5827_5841dupGATGGCAATGGAAGT​(p.Ser1947_Ser1948insAspGlyAsnGlySer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DMXL2 NM_001378457.1 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

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]

ENSG00000259678 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001378457.1.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMXL2	NM_001378457.1	c.5827_5841dupGATGGCAATGGAAGT	p.Ser1947_Ser1948insAspGlyAsnGlySer	conservative_inframe_insertion	Exon 24 of 44	ENST00000560891.6	NP_001365386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMXL2	ENST00000560891.6	c.5827_5841dupGATGGCAATGGAAGT	p.Ser1947_Ser1948insAspGlyAsnGlySer	conservative_inframe_insertion	Exon 24 of 44	1	NM_001378457.1	ENSP00000453267.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs606231461; hg19: chr15-51773461;