12-63626530-TA-TAA

Position:

• chr12-63626530-TA-TAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_173812.5(DPY19L2):​c.804-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (1924 hom., cov: 0)
  • Exomes 𝑓: 0.15 (1506 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPY19L2 NM_173812.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

Genes affected

DPY19L2 (HGNC:19414): (dpy-19 like 2) The protein encoded by this gene belongs to the dpy-19 family. It is highly expressed in testis, and is required for sperm head elongation and acrosome formation during spermatogenesis. Mutations in this gene are associated with an infertility disorder, spermatogenic failure type 9 (SPGF9). [provided by RefSeq, Dec 2011]

ENSG00000249753 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L2	NM_173812.5	c.804-5dupT		splice_region_variant, intron_variant		ENST00000324472.9	NP_776173.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPY19L2	ENST00000324472.9	c.804-5dupT		splice_region_variant, intron_variant		1	NM_173812.5	ENSP00000315988.4
DPY19L2	ENST00000306389.7	n.*287-5dupT		splice_region_variant, intron_variant		1		ENSP00000445878.1
ENSG00000249753	ENST00000509615.2	n.239-2707dupT		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.167 AC: 21082 AN: 126596 Hom.: 1923 Cov.: 0

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.165

GnomAD3 exomes AF: 0.148 AC: 13813 AN: 93570 Hom.: 1148 AF XY: 0.147 AC XY: 7622 AN XY: 51912

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.139

Gnomad SAS exome AF: 0.165

Gnomad FIN exome AF: 0.145

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.158

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.155 AC: 171860 AN: 1109180 Hom.: 1506 Cov.: 33 AF XY: 0.153 AC XY: 84044 AN XY: 548300

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.166 AC: 21075 AN: 126580 Hom.: 1924 Cov.: 0 AF XY: 0.162 AC XY: 9806 AN XY: 60386

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs371578418; hg19: chr12-64020310;