6-39864487-C-G

Variant names:

• chr6-39864487-C-G
• rs376069544
• NM_001201427.2:c.313C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001201427.2(DAAM2):​c.313C>G​(p.Arg105Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R105H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DAAM2 NM_001201427.2 missense
• Clinical Significance: Not reported in ClinVar
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.878

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM2	NM_001201427.2	c.313C>G	p.Arg105Gly	missense_variant	Exon 4 of 25	ENST00000274867.9	NP_001188356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9	c.313C>G	p.Arg105Gly	missense_variant	Exon 4 of 25	1	NM_001201427.2	ENSP00000274867.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T;D;.;D
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;.;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.88	D;D;D;D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Benign	1.8	.;L;L;L
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.5	.;D;D;D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0040	.;D;D;D
Sift4G	Uncertain	0.020	D;D;D;D
Polyphen		0.96	.;P;.;P
Vest4		0.68
MutPred		0.69		Gain of catalytic residue at M109 (P = 0.0332);Gain of catalytic residue at M109 (P = 0.0332);Gain of catalytic residue at M109 (P = 0.0332);Gain of catalytic residue at M109 (P = 0.0332);
MVP		0.67
MPC		0.73
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.63
gMVP		0.76

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

Other links and lift over

dbSNP: rs376069544; hg19: chr6-39832263;