rs2146009

Positions:

• chr14-59208145-T-A
• chr14-59208145-T-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+19377T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,116 control chromosomes in the GnomAD database, including 5,392 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 0.25 (5392 hom., cov: 32)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.-38+19377T>A		intron_variant		ENST00000360909.8	NP_001257449.1
DAAM1	XM_005267430.3	c.-38+19377T>A		intron_variant			XP_005267487.1
DAAM1	XM_005267431.2	c.-38+19231T>A		intron_variant			XP_005267488.1
DAAM1	XM_047431135.1	c.-38+19231T>A		intron_variant			XP_047287091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAAM1	ENST00000360909.8	c.-38+19377T>A		intron_variant		1	NM_001270520.2	ENSP00000354162	P1
DAAM1	ENST00000556596.1	n.123+19377T>A		intron_variant, non_coding_transcript_variant		1
DAAM1	ENST00000556135.1	c.-38+19377T>A		intron_variant		3		ENSP00000450498

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38684 AN: 151998 Hom.: 5380 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.255 AC: 38719 AN: 152116 Hom.: 5392 Cov.: 32 AF XY: 0.254 AC XY: 18910 AN XY: 74378

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.271

Alfa AF: 0.243 Hom.: 586

Bravo AF: 0.271

Asia WGS AF: 0.395 AC: 1372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2146009; hg19: chr14-59674863;