chr14-59290284-C-T

Variant names:

• chr14-59290284-C-T
• rs7155987
• NM_001270520.2:c.184-933C>T

Variant summary

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

The NM_001270520.2(DAAM1):​c.184-933C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,136 control chromosomes in the GnomAD database, including 1,568 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 0.12 (1568 hom., cov: 32)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.184-933C>T		intron_variant	Intron 2 of 24	ENST00000360909.8	NP_001257449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM1	ENST00000360909.8	c.184-933C>T		intron_variant	Intron 2 of 24	1	NM_001270520.2	ENSP00000354162.3
DAAM1	ENST00000395125.1	c.184-933C>T		intron_variant	Intron 1 of 24	1		ENSP00000378557.1
DAAM1	ENST00000556135.1	c.184-933C>T		intron_variant	Intron 2 of 2	3		ENSP00000450498.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18332 AN: 152018 Hom.: 1567 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.120 AC: 18332 AN: 152136 Hom.: 1568 Cov.: 32 AF XY: 0.121 AC XY: 9020 AN XY: 74346

African (AFR) AF: 0.0363 AC: 1507 AN: 41530

American (AMR) AF: 0.140 AC: 2141 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2067 AN: 5168

South Asian (SAS) AF: 0.137 AC: 661 AN: 4818

European-Finnish (FIN) AF: 0.120 AC: 1268 AN: 10572

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9948 AN: 67990

Other (OTH) AF: 0.137 AC: 289 AN: 2112

Alfa AF: 0.0989 Hom.: 301

Bravo AF: 0.123

Asia WGS AF: 0.252 AC: 875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.37
DANN	Benign	0.58
PhyloP100		-1.0
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: rs7155987; hg19: chr14-59757002;