chr6-39867821-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001201427.2(DAAM2):c.740C>T(p.Ala247Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,449,212 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
DAAM2
NM_001201427.2 missense
NM_001201427.2 missense
Scores
4
8
3
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
DAAM2 (HGNC:18143): (dishevelled associated activator of morphogenesis 2) Predicted to enable actin binding activity and small GTPase binding activity. Predicted to be involved in nervous system development and regulation of Wnt signaling pathway. Predicted to act upstream of or within determination of left/right symmetry. Located in extracellular exosome. [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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DAAM2 | NM_001201427.2 | c.740C>T | p.Ala247Val | missense_variant | 6/25 | ENST00000274867.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DAAM2 | ENST00000274867.9 | c.740C>T | p.Ala247Val | missense_variant | 6/25 | 1 | NM_001201427.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000224 AC: 5AN: 223698Hom.: 0 AF XY: 0.0000246 AC XY: 3AN XY: 121724
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000276 AC: 4AN: 1449212Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 2AN XY: 719888
GnomAD4 exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ExAC
?
AF:
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2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 13, 2023 | The c.740C>T (p.A247V) alteration is located in exon 6 (coding exon 5) of the DAAM2 gene. This alteration results from a C to T substitution at nucleotide position 740, causing the alanine (A) at amino acid position 247 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;D;.;D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
T
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;D;.;D
Vest4
MutPred
Loss of phosphorylation at Y246 (P = 0.1955);Loss of phosphorylation at Y246 (P = 0.1955);Loss of phosphorylation at Y246 (P = 0.1955);Loss of phosphorylation at Y246 (P = 0.1955);
MVP
0.68
MPC
0.64
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
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