rs1252989

chr14-59212468-A-Gchr14-59212468-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAAM1	NM_001270520.2	c.-38+23700A>G		intron_variant		ENST00000360909.8
DAAM1	XM_005267430.3	c.-38+23700A>G		intron_variant
DAAM1	XM_005267431.2	c.-38+23554A>G		intron_variant
DAAM1	XM_047431135.1	c.-38+23554A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAAM1	ENST00000360909.8	c.-38+23700A>G		intron_variant		1	NM_001270520.2	P1
DAAM1	ENST00000556596.1	n.123+23700A>G		intron_variant, non_coding_transcript_variant		1
DAAM1	ENST00000556135.1	c.-38+23700A>G		intron_variant		3

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

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.416

Alfa AF: 0.436 Hom.: 2323

Bravo AF: 0.418

Asia WGS AF: 0.367 AC: 1280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.6
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1252989; hg19: chr14-59679186;