chr6-39860979-C-A

Variant names:

• chr6-39860979-C-A
• rs370112679
• NM_001201427.2:c.220C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001201427.2(DAAM2):​c.220C>A​(p.Pro74Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,613,048 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000056 (1 hom.)
• Consequence: DAAM2 NM_001201427.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 2.47
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024380147).

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.220C>A	p.Pro74Thr	missense	Exon 3 of 25	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.220C>A	p.Pro74Thr	missense	Exon 3 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.220C>A	p.Pro74Thr	missense	Exon 3 of 25	ENSP00000274867.4	Q86T65-3
	DAAM2	ENST00000538976.5	TSL:1	c.220C>A	p.Pro74Thr	missense	Exon 3 of 25	ENSP00000437808.1	Q86T65-4
	DAAM2	ENST00000405961.3	TSL:1	c.220C>A	p.Pro74Thr	missense	Exon 3 of 3	ENSP00000384637.3	F2Z2Q2

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000848 AC: 21 AN: 247640 AF XY: 0.0000819

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000726

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000561 AC: 82 AN: 1460850 Hom.: 1 Cov.: 31 AF XY: 0.0000537 AC XY: 39 AN XY: 726580

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39676

South Asian (SAS) AF: 0.000233 AC: 20 AN: 85852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111612

Other (OTH) AF: 0.000597 AC: 36 AN: 60350

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74420

African (AFR) AF: 0.00 AC: 0 AN: 41520

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000968 AC: 5 AN: 5166

South Asian (SAS) AF: 0.00146 AC: 7 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000171 Hom.: 0

ExAC AF: 0.0000745 AC: 9

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	DAAM2-related disorder (1)
-	1	-	Inborn genetic diseases (1)
-	1	-	Nephrotic syndrome, type 24 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.029
Eigen_PC	Benign	0.028
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.024	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.27
Sift	Benign	0.20	T
Sift4G	Benign	0.33	T
Polyphen		0.080	B
Vest4		0.38
MutPred		0.54		Loss of catalytic residue at P73 (P = 0.0121)
MVP		0.68
MPC		0.24
ClinPred		0.042	T
GERP RS		5.3
Varity_R		0.12
gMVP		0.58
Mutation Taster		=65/35	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: rs370112679; hg19: chr6-39828755;