rs1270988

Positions:

• chr14-59217516-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270520.2(DAAM1):​c.-38+28748A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,894 control chromosomes in the GnomAD database, including 13,847 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 (13847 hom., cov: 31)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.-38+28748A>C		intron_variant		ENST00000360909.8	NP_001257449.1
DAAM1	XM_005267430.3	c.-38+28748A>C		intron_variant			XP_005267487.1
DAAM1	XM_005267431.2	c.-38+28602A>C		intron_variant			XP_005267488.1
DAAM1	XM_047431135.1	c.-38+28602A>C		intron_variant			XP_047287091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAAM1	ENST00000360909.8	c.-38+28748A>C		intron_variant		1	NM_001270520.2	ENSP00000354162	P1
DAAM1	ENST00000556596.1	n.123+28748A>C		intron_variant, non_coding_transcript_variant		1
DAAM1	ENST00000556135.1	c.-38+28748A>C		intron_variant		3		ENSP00000450498

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64616 AN: 151776 Hom.: 13819 Cov.: 31

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.426 AC: 64698 AN: 151894 Hom.: 13847 Cov.: 31 AF XY: 0.428 AC XY: 31779 AN XY: 74232

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.416

Alfa AF: 0.435 Hom.: 2299

Bravo AF: 0.417

Asia WGS AF: 0.364 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.070
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1270988; hg19: chr14-59684234;