12-63626530-TA-TAAAA

Variant names:

• chr12-63626530-T-TAAA
• rs371578418
• NM_173812.5:c.804-7_804-5dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_173812.5(DPY19L2):​c.804-7_804-5dupTTT 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 0.024 (80 hom., cov: 0)
  • Exomes 𝑓: 0.026 (242 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPY19L2 NM_173812.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702
• Publications: 1 publications found

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]

DPY19L2 Gene-Disease associations (from GenCC):

• spermatogenic failure 9

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• male infertility due to globozoospermia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000249753 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3042 AN: 127026 Hom.: 80 Cov.: 0

Gnomad AFR AF: 0.00732

Gnomad AMI AF: 0.0315

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0257

Gnomad EAS AF: 0.0831

Gnomad SAS AF: 0.0127

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.00758

Gnomad NFE AF: 0.0316

Gnomad OTH AF: 0.0170

GnomAD2 exomes AF: 0.0228 AC: 2138 AN: 93570 AF XY: 0.0214

Gnomad AFR exome AF: 0.0264

Gnomad AMR exome AF: 0.0334

Gnomad ASJ exome AF: 0.0234

Gnomad EAS exome AF: 0.0601

Gnomad FIN exome AF: 0.0124

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.0279

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0263 AC: 30985 AN: 1178868 Hom.: 242 Cov.: 33 AF XY: 0.0262 AC XY: 15274 AN XY: 582806

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0143 AC: 351 AN: 24542

American (AMR) AF: 0.0253 AC: 553 AN: 21884

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 533 AN: 19258

East Asian (EAS) AF: 0.0528 AC: 1520 AN: 28800

South Asian (SAS) AF: 0.0324 AC: 1965 AN: 60566

European-Finnish (FIN) AF: 0.0202 AC: 790 AN: 39048

Middle Eastern (MID) AF: 0.0162 AC: 69 AN: 4266

European-Non Finnish (NFE) AF: 0.0257 AC: 23941 AN: 932392

Other (OTH) AF: 0.0263 AC: 1263 AN: 48112

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0240 AC: 3043 AN: 127012 Hom.: 80 Cov.: 0 AF XY: 0.0229 AC XY: 1389 AN XY: 60610

African (AFR) AF: 0.00735 AC: 232 AN: 31584

American (AMR) AF: 0.0147 AC: 183 AN: 12478

Ashkenazi Jewish (ASJ) AF: 0.0257 AC: 84 AN: 3266

East Asian (EAS) AF: 0.0834 AC: 357 AN: 4280

South Asian (SAS) AF: 0.0127 AC: 52 AN: 4084

European-Finnish (FIN) AF: 0.0181 AC: 115 AN: 6364

Middle Eastern (MID) AF: 0.00826 AC: 2 AN: 242

European-Non Finnish (NFE) AF: 0.0316 AC: 1962 AN: 62144

Other (OTH) AF: 0.0169 AC: 29 AN: 1712

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs371578418; hg19: chr12-64020310;