chr12-63582515-T-C

Position:

• chr12-63582515-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173812.5(DPY19L2):​c.1616A>G​(p.His539Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DPY19L2 NM_173812.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.36

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L2	NM_173812.5	c.1616A>G	p.His539Arg	missense_variant	18/22	ENST00000324472.9	NP_776173.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPY19L2	ENST00000324472.9	c.1616A>G	p.His539Arg	missense_variant	18/22	1	NM_173812.5	ENSP00000315988.4
DPY19L2	ENST00000413230.6	n.362A>G		non_coding_transcript_exon_variant	2/6	2
DPY19L2	ENST00000439061.6	n.*77A>G		non_coding_transcript_exon_variant	8/11	5		ENSP00000437474.1
DPY19L2	ENST00000439061.6	n.*77A>G		3_prime_UTR_variant	8/11	5		ENSP00000437474.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spermatogenic failure 9 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

MGZ Medical Genetics Center

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.075
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.68		Gain of catalytic residue at Q542 (P = 0.0485);
MVP		0.57
MPC		0.76
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.56
gMVP		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-63976295;