rs941882

Variant names:

• chr14-59324911-A-C
• rs941882
• NM_001270520.2:c.989+457A>C

Variant summary

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

The NM_001270520.2(DAAM1):​c.989+457A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,970 control chromosomes in the GnomAD database, including 7,380 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 0.30 (7380 hom., cov: 32)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 9 publications found

Genes affected

DAAM1 (HGNC:18142): (dishevelled associated activator of morphogenesis 1) Cell motility, adhesion, cytokinesis, and other functions of the cell cortex are mediated by reorganization of the actin cytoskeleton and several formin homology (FH) proteins have been associated with these processes. The protein encoded by this gene contains two FH domains and belongs to a novel FH protein subfamily implicated in cell polarity. A key regulator of cytoskeletal architecture, the small GTPase Rho, is activated during development by Wnt/Fz signaling to control cell polarity and movement. The protein encoded by this gene is thought to function as a scaffolding protein for the Wnt-induced assembly of a disheveled (Dvl)-Rho complex. This protein also promotes the nucleation and elongation of new actin filaments and regulates cell growth through the stabilization of microtubules. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.989+457A>C		intron_variant	Intron 8 of 24	ENST00000360909.8	NP_001257449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM1	ENST00000360909.8	c.989+457A>C		intron_variant	Intron 8 of 24	1	NM_001270520.2	ENSP00000354162.3
DAAM1	ENST00000395125.1	c.989+457A>C		intron_variant	Intron 7 of 24	1		ENSP00000378557.1
DAAM1	ENST00000556894.1	n.105+457A>C		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45515 AN: 151852 Hom.: 7368 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.300 AC: 45574 AN: 151970 Hom.: 7380 Cov.: 32 AF XY: 0.296 AC XY: 21997 AN XY: 74282

African (AFR) AF: 0.418 AC: 17308 AN: 41408

American (AMR) AF: 0.349 AC: 5338 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3472

East Asian (EAS) AF: 0.107 AC: 553 AN: 5170

South Asian (SAS) AF: 0.257 AC: 1237 AN: 4820

European-Finnish (FIN) AF: 0.212 AC: 2239 AN: 10556

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17058 AN: 67950

Other (OTH) AF: 0.300 AC: 634 AN: 2110

Alfa AF: 0.274 Hom.: 19180

Bravo AF: 0.314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.4
DANN	Benign	0.32
PhyloP100		-0.18
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: rs941882; hg19: chr14-59791629;