12-63560538-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_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. 16/21 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

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0360
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 id is 3505059.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DPY19L2NM_173812.5 linkc.2251G>A p.Val751Met missense_variant 22/22 ENST00000324472.9 NP_776173.3 Q6NUT2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DPY19L2ENST00000324472.9 linkc.2251G>A p.Val751Met missense_variant 22/221 NM_173812.5 ENSP00000315988.4 Q6NUT2-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsSep 24, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1876265347; hg19: chr12-63954318; API