chr7-140544711-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015689.5(DENND2A):c.2234C>T(p.Ser745Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,378 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
DENND2A
NM_015689.5 missense
NM_015689.5 missense
Scores
10
8
Clinical Significance
Conservation
PhyloP100: 3.61
Genes affected
Genome browser will be placed here
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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DENND2A | NM_015689.5 | c.2234C>T | p.Ser745Phe | missense_variant | 14/20 | ENST00000496613.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DENND2A | ENST00000496613.6 | c.2234C>T | p.Ser745Phe | missense_variant | 14/20 | 2 | NM_015689.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000163 AC: 4AN: 245492Hom.: 0 AF XY: 0.0000225 AC XY: 3AN XY: 133294
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460378Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4AN XY: 726322
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
AC:
1
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 | Nov 02, 2023 | The c.2234C>T (p.S745F) alteration is located in exon 12 (coding exon 12) of the DENND2A gene. This alteration results from a C to T substitution at nucleotide position 2234, causing the serine (S) at amino acid position 745 to be replaced by a phenylalanine (F). 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
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;T;D
Sift4G
Uncertain
T;T;T;.;D
Polyphen
P;P;P;.;D
Vest4
MutPred
Loss of disorder (P = 0.0064);Loss of disorder (P = 0.0064);Loss of disorder (P = 0.0064);.;Loss of disorder (P = 0.0064);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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