12-63626530-TA-TAAAAA

Position:

• chr12-63626530-TA-TAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_173812.5(DPY19L2):​c.804-8_804-5dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0029 (39 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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000236 (30/127298) while in subpopulation EAS AF= 0.00185 (8/4316). AF 95% confidence interval is 0.000922. There are 0 homozygotes in gnomad4. There are 19 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L2	NM_173812.5	c.804-8_804-5dupTTTT		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.804-8_804-5dupTTTT		splice_region_variant, intron_variant		1	NM_173812.5	ENSP00000315988.4
DPY19L2	ENST00000306389.7	n.*287-8_*287-5dupTTTT		splice_region_variant, intron_variant		1		ENSP00000445878.1
ENSG00000249753	ENST00000509615.2	n.239-2710_239-2707dupTTTT		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.000236 AC: 30 AN: 127312 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00464

Gnomad AMR AF: 0.000320

Gnomad ASJ AF: 0.000305

Gnomad EAS AF: 0.00185

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00379

Gnomad NFE AF: 0.000193

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00520 AC: 487 AN: 93570 Hom.: 33 AF XY: 0.00489 AC XY: 254 AN XY: 51912

Gnomad AFR exome AF: 0.00563

Gnomad AMR exome AF: 0.00693

Gnomad ASJ exome AF: 0.00355

Gnomad EAS exome AF: 0.0188

Gnomad SAS exome AF: 0.00553

Gnomad FIN exome AF: 0.00194

Gnomad NFE exome AF: 0.00373

Gnomad OTH exome AF: 0.00686

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00290 AC: 3519 AN: 1212928 Hom.: 39 Cov.: 33 AF XY: 0.00300 AC XY: 1797 AN XY: 599868

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00493

Gnomad4 ASJ exome AF: 0.00396

Gnomad4 EAS exome AF: 0.00765

Gnomad4 SAS exome AF: 0.00606

Gnomad4 FIN exome AF: 0.00273

Gnomad4 NFE exome AF: 0.00251

Gnomad4 OTH exome AF: 0.00328

GnomAD4 genome AF: 0.000236 AC: 30 AN: 127298 Hom.: 0 Cov.: 0 AF XY: 0.000313 AC XY: 19 AN XY: 60752

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000320

Gnomad4 ASJ AF: 0.000305

Gnomad4 EAS AF: 0.00185

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000193

Gnomad4 OTH AF: 0.00

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: rs371578418; hg19: chr12-64020310;