NM_001270520.2:c.-38+23700A>G

Variant names:

• chr14-59212468-A-G
• rs1252989
• NM_001270520.2:c.-38+23700A>G

Variant summary

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

The NM_001270520.2(DAAM1):​c.-38+23700A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,152 control chromosomes in the GnomAD database, including 13,939 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 0.43 (13939 hom., cov: 33)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270520.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM1	NM_001270520.2	MANE Select	c.-38+23700A>G		intron	N/A	NP_001257449.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM1	ENST00000360909.8	TSL:1 MANE Select	c.-38+23700A>G		intron	N/A	ENSP00000354162.3
	DAAM1	ENST00000556596.1	TSL:1	n.123+23700A>G		intron	N/A
	DAAM1	ENST00000556135.1	TSL:3	c.-38+23700A>G		intron	N/A	ENSP00000450498.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64861 AN: 152034 Hom.: 13912 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.427 AC: 64939 AN: 152152 Hom.: 13939 Cov.: 33 AF XY: 0.429 AC XY: 31914 AN XY: 74392

African (AFR) AF: 0.424 AC: 17571 AN: 41488

American (AMR) AF: 0.397 AC: 6073 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1548 AN: 3468

East Asian (EAS) AF: 0.348 AC: 1805 AN: 5184

South Asian (SAS) AF: 0.393 AC: 1897 AN: 4826

European-Finnish (FIN) AF: 0.470 AC: 4970 AN: 10576

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29629 AN: 68004

Other (OTH) AF: 0.416 AC: 877 AN: 2106

Alfa AF: 0.426 Hom.: 4518

Bravo AF: 0.418

Asia WGS AF: 0.367 AC: 1280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.65
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1252989; hg19: chr14-59679186;