2-158815811-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001017920.3(DAPL1):c.314G>A(p.Arg105Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000429 in 1,609,924 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000045 ( 0 hom. )
Consequence
DAPL1
NM_001017920.3 missense
NM_001017920.3 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 6.39
Genes affected
DAPL1 (HGNC:21490): (death associated protein like 1) Predicted to enable death domain binding activity. Predicted to be involved in apoptotic signaling pathway; cellular response to amino acid starvation; and negative regulation of autophagy. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DAPL1 | ENST00000309950.8 | c.314G>A | p.Arg105Gln | missense_variant | 4/4 | 1 | NM_001017920.3 | ENSP00000309538.4 | ||
DAPL1 | ENST00000621326.4 | c.*28G>A | 3_prime_UTR_variant | 5/5 | 1 | ENSP00000479872.1 | ||||
DAPL1 | ENST00000343761.4 | c.132+8696G>A | intron_variant | 3 | ENSP00000385306.2 | |||||
DAPL1 | ENST00000409042.5 | c.207+8696G>A | intron_variant | 4 | ENSP00000386422.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152184Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251414Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135884
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GnomAD4 exome AF: 0.0000453 AC: 66AN: 1457740Hom.: 0 Cov.: 29 AF XY: 0.0000469 AC XY: 34AN XY: 725542
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74338
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 24, 2023 | The c.314G>A (p.R105Q) alteration is located in exon 4 (coding exon 4) of the DAPL1 gene. This alteration results from a G to A substitution at nucleotide position 314, causing the arginine (R) at amino acid position 105 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Loss of MoRF binding (P = 0.0093);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at