NM_001270520.2:c.2160+1685A>G

Variant names:

• chr14-59349308-A-G
• rs17834014
• NM_001270520.2:c.2160+1685A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001270520.2(DAAM1):​c.2160+1685A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 152,368 control chromosomes in the GnomAD database, including 376 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 0.062 (376 hom., cov: 33)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 7 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.2160+1685A>G		intron_variant	Intron 17 of 24	ENST00000360909.8	NP_001257449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM1	ENST00000360909.8	c.2160+1685A>G		intron_variant	Intron 17 of 24	1	NM_001270520.2	ENSP00000354162.3
DAAM1	ENST00000395125.1	c.2190+1685A>G		intron_variant	Intron 17 of 24	1		ENSP00000378557.1
DAAM1	ENST00000553966.5	n.77+1685A>G		intron_variant	Intron 1 of 7	2
DAAM1	ENST00000554459.5	n.379+1685A>G		intron_variant	Intron 4 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 9372 AN: 152250 Hom.: 375 Cov.: 33

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0878

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0904

Gnomad OTH AF: 0.0608

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

GnomAD4 genome AF: 0.0616 AC: 9379 AN: 152368 Hom.: 376 Cov.: 33 AF XY: 0.0607 AC XY: 4520 AN XY: 74514

African (AFR) AF: 0.0156 AC: 650 AN: 41594

American (AMR) AF: 0.0559 AC: 855 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0752 AC: 261 AN: 3472

East Asian (EAS) AF: 0.0125 AC: 65 AN: 5194

South Asian (SAS) AF: 0.0513 AC: 248 AN: 4830

European-Finnish (FIN) AF: 0.0878 AC: 933 AN: 10624

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0904 AC: 6149 AN: 68036

Other (OTH) AF: 0.0634 AC: 134 AN: 2112

Alfa AF: 0.0807 Hom.: 887

Bravo AF: 0.0568

Asia WGS AF: 0.0510 AC: 176 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		1.1
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: rs17834014; hg19: chr14-59816026;