12-63626530-TA-TAAAAA

Variant names:

• chr12-63626530-T-TAAAA
• rs371578418
• NM_173812.5:c.804-8_804-5dupTTTT

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 rank	MANE	Protein	UniProt
DPY19L2	NM_173812.5	c.804-8_804-5dupTTTT		splice_region_variant, intron_variant	Intron 6 of 21	ENST00000324472.9	NP_776173.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPY19L2	ENST00000324472.9	c.804-5_804-4insTTTT		splice_region_variant, intron_variant	Intron 6 of 21	1	NM_173812.5	ENSP00000315988.4
DPY19L2	ENST00000306389.7	n.*287-5_*287-4insTTTT		splice_region_variant, intron_variant	Intron 5 of 13	1		ENSP00000445878.1
ENSG00000249753	ENST00000509615.2	n.239-2707_239-2706insTTTT		intron_variant	Intron 1 of 1	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;