rs7143698

Variant names:

• chr14-59337409-G-A
• rs7143698
• NM_001270520.2:c.1969-2665G>A

Variant summary

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

The NM_001270520.2(DAAM1):​c.1969-2665G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,086 control chromosomes in the GnomAD database, including 4,549 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 0.24 (4549 hom., cov: 32)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.1969-2665G>A		intron_variant	Intron 15 of 24	ENST00000360909.8	NP_001257449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM1	ENST00000360909.8	c.1969-2665G>A		intron_variant	Intron 15 of 24	1	NM_001270520.2	ENSP00000354162.3
DAAM1	ENST00000395125.1	c.1969-976G>A		intron_variant	Intron 14 of 24	1		ENSP00000378557.1
DAAM1	ENST00000554459.5	n.188-2665G>A		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35840 AN: 151968 Hom.: 4528 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.236 AC: 35913 AN: 152086 Hom.: 4549 Cov.: 32 AF XY: 0.235 AC XY: 17495 AN XY: 74342

African (AFR) AF: 0.335 AC: 13878 AN: 41464

American (AMR) AF: 0.238 AC: 3635 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3466

East Asian (EAS) AF: 0.184 AC: 951 AN: 5172

South Asian (SAS) AF: 0.221 AC: 1065 AN: 4814

European-Finnish (FIN) AF: 0.160 AC: 1689 AN: 10586

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13068 AN: 67990

Other (OTH) AF: 0.216 AC: 455 AN: 2110

Alfa AF: 0.200 Hom.: 5054

Bravo AF: 0.246

Asia WGS AF: 0.218 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.42
PhyloP100		0.61
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: rs7143698; hg19: chr14-59804127;