chr12-63560538-C-T

Variant names:

• chr12-63560538-C-T
• rs1876265347
• NM_173812.5:c.2251G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_173812.5(DPY19L2):​c.2251G>A​(p.Val751Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DPY19L2 NM_173812.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0360
• Publications: 0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• male infertility due to globozoospermia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07238668).
• BP6: Variant 12-63560538-C-T is Benign according to our data. Variant chr12-63560538-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3505059.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173812.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPY19L2	NM_173812.5	MANE Select	c.2251G>A	p.Val751Met	missense	Exon 22 of 22	NP_776173.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPY19L2	ENST00000324472.9	TSL:1 MANE Select	c.2251G>A	p.Val751Met	missense	Exon 22 of 22	ENSP00000315988.4	Q6NUT2-1
	DPY19L2	ENST00000882292.1		c.2191G>A	p.Val731Met	missense	Exon 21 of 21	ENSP00000552351.1
	DPY19L2	ENST00000961037.1		c.2179G>A	p.Val727Met	missense	Exon 20 of 20	ENSP00000631096.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.2
DANN	Benign	0.94
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.80	N
PhyloP100		-0.036
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.047
Sift	Benign	0.19	T
Sift4G	Benign	0.25	T
Polyphen		0.24	B
Vest4		0.050
MutPred		0.53		Gain of catalytic residue at F747 (P = 0.0057)
MVP		0.21
MPC		0.20
ClinPred		0.39	T
GERP RS		0.39
Varity_R		0.049
gMVP		0.67
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1876265347; hg19: chr12-63954318;