6-39856313-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001201427.2(DAAM2):c.11G>T(p.Arg4Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DAAM2 NM_001201427.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.55

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 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.11G>T	p.Arg4Leu	missense_variant	2/25	ENST00000274867.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAAM2	ENST00000274867.9	c.11G>T	p.Arg4Leu	missense_variant	2/25	1	NM_001201427.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1384024 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 683096

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2023

The c.11G>T (p.R4L) alteration is located in exon 2 (coding exon 1) of the DAAM2 gene. This alteration results from a G to T substitution at nucleotide position 11, causing the arginine (R) at amino acid position 4 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.086	T;T;.;T;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;.;D;D;D
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-0.32	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.60	T
Sift4G	Uncertain	0.025	D;D;D;D;D
Polyphen		0.099, 0.71	.;B;.;B;P
Vest4		0.60
MutPred		0.23		Loss of methylation at R4 (P = 0.0209);Loss of methylation at R4 (P = 0.0209);Loss of methylation at R4 (P = 0.0209);Loss of methylation at R4 (P = 0.0209);Loss of methylation at R4 (P = 0.0209);
MVP		0.55
MPC		0.19
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.26
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-39824089;