rs3008798

Variant names:

• chr6-39812086-A-C
• rs3008798
• NM_001201427.2:c.-57+19621A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001201427.2(DAAM2):​c.-57+19621A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,044 control chromosomes in the GnomAD database, including 17,825 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (17825 hom., cov: 32)
• Consequence: DAAM2 NM_001201427.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 2 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 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 24

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000308921 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM2	NM_001201427.2	c.-57+19621A>C		intron_variant	Intron 1 of 24	ENST00000274867.9	NP_001188356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9	c.-57+19621A>C		intron_variant	Intron 1 of 24	1	NM_001201427.2	ENSP00000274867.4

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71282 AN: 151926 Hom.: 17816 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.473

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.469 AC: 71326 AN: 152044 Hom.: 17825 Cov.: 32 AF XY: 0.469 AC XY: 34892 AN XY: 74324

African (AFR) AF: 0.330 AC: 13688 AN: 41470

American (AMR) AF: 0.522 AC: 7980 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1879 AN: 3468

East Asian (EAS) AF: 0.138 AC: 711 AN: 5168

South Asian (SAS) AF: 0.609 AC: 2931 AN: 4816

European-Finnish (FIN) AF: 0.508 AC: 5356 AN: 10544

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37048 AN: 67974

Other (OTH) AF: 0.469 AC: 991 AN: 2114

Alfa AF: 0.528 Hom.: 12993

Bravo AF: 0.458

Asia WGS AF: 0.401 AC: 1396 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.34
PhyloP100		0.0030
Mutation Taster		=100/0	polymorphism (auto)

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: rs3008798; hg19: chr6-39779862;