chr12-63597906-C-T

Variant names:

• chr12-63597906-C-T
• rs147328742
• NM_173812.5:c.1364G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173812.5(DPY19L2):​c.1364G>A​(p.Arg455His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000189 in 1,589,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: DPY19L2 NM_173812.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08287004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPY19L2	NM_173812.5	c.1364G>A	p.Arg455His	missense_variant	Exon 14 of 22	ENST00000324472.9	NP_776173.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPY19L2	ENST00000324472.9	c.1364G>A	p.Arg455His	missense_variant	Exon 14 of 22	1	NM_173812.5	ENSP00000315988.4

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151722 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000953

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000300 AC: 7 AN: 233582 Hom.: 0 AF XY: 0.0000315 AC XY: 4 AN XY: 127042

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000110

Gnomad EAS exome AF: 0.000115

Gnomad SAS exome AF: 0.0000369

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000277

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000167 AC: 24 AN: 1437162 Hom.: 0 Cov.: 28 AF XY: 0.0000168 AC XY: 12 AN XY: 715004

Gnomad4 AFR exome AF: 0.0000621

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000396

Gnomad4 EAS exome AF: 0.000102

Gnomad4 SAS exome AF: 0.0000489

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.00000908

Gnomad4 OTH exome AF: 0.0000337

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151840 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74192

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000953

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000340

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.21
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	5.1	N;N
REVEL	Benign	0.073
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;.
Polyphen		0.0040	B;.
Vest4		0.19
MutPred		0.57		Gain of catalytic residue at D452 (P = 0);.;
MVP		0.13
MPC		0.22
ClinPred		0.071	T
GERP RS		0.055
Varity_R		0.024
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs147328742; hg19: chr12-63991686; COSMIC: COSV100116775;