6-39856353-C-A

Variant names:

• chr6-39856353-C-A
• rs376650953
• NM_001201427.2:c.51C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001201427.2(DAAM2):​c.51C>A​(p.Phe17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,206 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F17F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: DAAM2 NM_001201427.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 0 publications found

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]

DAAM2-AS1 (HGNC:40830): (DAAM2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201427.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	NM_001201427.2	MANE Select	c.51C>A	p.Phe17Leu	missense	Exon 2 of 25	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.51C>A	p.Phe17Leu	missense	Exon 2 of 25	NP_056160.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	ENST00000274867.9	TSL:1 MANE Select	c.51C>A	p.Phe17Leu	missense	Exon 2 of 25	ENSP00000274867.4	Q86T65-3
	DAAM2	ENST00000538976.5	TSL:1	c.51C>A	p.Phe17Leu	missense	Exon 2 of 25	ENSP00000437808.1	Q86T65-4
	DAAM2	ENST00000405961.3	TSL:1	c.51C>A	p.Phe17Leu	missense	Exon 2 of 3	ENSP00000384637.3	F2Z2Q2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1401206 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 692540

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31282

American (AMR) AF: 0.00 AC: 0 AN: 36548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24676

East Asian (EAS) AF: 0.00 AC: 0 AN: 34936

South Asian (SAS) AF: 0.00 AC: 0 AN: 77780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1081446

Other (OTH) AF: 0.00 AC: 0 AN: 58140

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	2.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		-1.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.52
Sift	Benign	0.22	T
Sift4G	Benign	0.19	T
Polyphen		0.98	D
Vest4		0.64
MutPred		0.56		Loss of sheet (P = 0.0126)
MVP		0.63
MPC		0.67
ClinPred		0.98	D
GERP RS		-9.1
Varity_R		0.23
gMVP		0.56
Mutation Taster		=51/49	polymorphism

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

Other links and lift over

dbSNP: rs376650953; hg19: chr6-39824129;