chr6-170283073-G-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_005618.4(DLL1):c.2081C>T(p.Ser694Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00022 in 1,614,080 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S694S) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00022 ( 1 hom. )
Consequence
DLL1
NM_005618.4 missense
NM_005618.4 missense
Scores
9
9
Clinical Significance
Conservation
PhyloP100: 7.31
Genes affected
DLL1 (HGNC:2908): (delta like canonical Notch ligand 1) DLL1 is a human homolog of the Notch Delta ligand and is a member of the delta/serrate/jagged family. It plays a role in mediating cell fate decisions during hematopoiesis. It may play a role in cell-to-cell communication. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 6-170283073-G-A is Benign according to our data. Variant chr6-170283073-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1552785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000177 (27/152300) while in subpopulation NFE AF= 0.000323 (22/68016). AF 95% confidence interval is 0.000218. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DLL1 | NM_005618.4 | c.2081C>T | p.Ser694Leu | missense_variant | 10/11 | ENST00000366756.4 | |
DLL1 | XM_005266934.5 | c.1484C>T | p.Ser495Leu | missense_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DLL1 | ENST00000366756.4 | c.2081C>T | p.Ser694Leu | missense_variant | 10/11 | 1 | NM_005618.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152182Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000175 AC: 44AN: 251426Hom.: 1 AF XY: 0.000147 AC XY: 20AN XY: 135890
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GnomAD4 exome AF: 0.000224 AC: 328AN: 1461780Hom.: 1 Cov.: 34 AF XY: 0.000209 AC XY: 152AN XY: 727176
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | DLL1: BP4, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 23, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
D
Sift4G
Uncertain
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
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