chr12-63582486-G-T

Position:

• chr12-63582486-G-T

Variant summary

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

The NM_173812.5(DPY19L2):​c.1645C>A​(p.Leu549Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.03

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPY19L2	NM_173812.5	c.1645C>A	p.Leu549Ile	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.1645C>A	p.Leu549Ile	missense_variant	18/22	1	NM_173812.5	ENSP00000315988.4
DPY19L2	ENST00000413230.6	n.391C>A		non_coding_transcript_exon_variant	2/6	2
DPY19L2	ENST00000439061.6	n.*106C>A		non_coding_transcript_exon_variant	8/11	5		ENSP00000437474.1
DPY19L2	ENST00000439061.6	n.*106C>A		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

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 08, 2022

The c.1645C>A (p.L549I) alteration is located in exon 18 (coding exon 18) of the DPY19L2 gene. This alteration results from a C to A substitution at nucleotide position 1645, causing the leucine (L) at amino acid position 549 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	0.10
Eigen_PC	Benign	-0.049
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.031	D
Polyphen		0.93	P
Vest4		0.60
MutPred		0.58		Gain of catalytic residue at A548 (P = 0.0014);
MVP		0.52
MPC		0.59
ClinPred		0.83	D
GERP RS		2.4
Varity_R		0.17
gMVP		0.67

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: chr12-63976266;