rs17095967

Variant names:

• chr14-59259085-G-A
• rs17095967
• NM_001270520.2:c.-37-4356G>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.-37-4356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,082 control chromosomes in the GnomAD database, including 5,228 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 (5228 hom., cov: 32)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.-37-4356G>A		intron_variant	Intron 1 of 24	ENST00000360909.8	NP_001257449.1
DAAM1	XM_005267430.3	c.-37-4356G>A		intron_variant	Intron 1 of 25		XP_005267487.1
DAAM1	XM_005267431.2	c.-37-4356G>A		intron_variant	Intron 1 of 25		XP_005267488.1
DAAM1	XM_047431135.1	c.-37-4356G>A		intron_variant	Intron 1 of 24		XP_047287091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM1	ENST00000360909.8	c.-37-4356G>A		intron_variant	Intron 1 of 24	1	NM_001270520.2	ENSP00000354162.3
DAAM1	ENST00000556596.1	n.124-4356G>A		intron_variant	Intron 1 of 1	1
DAAM1	ENST00000556135.1	c.-37-4356G>A		intron_variant	Intron 1 of 2	3		ENSP00000450498.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38251 AN: 151964 Hom.: 5219 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.252 AC: 38294 AN: 152082 Hom.: 5228 Cov.: 32 AF XY: 0.252 AC XY: 18723 AN XY: 74334

African (AFR) AF: 0.206 AC: 8562 AN: 41476

American (AMR) AF: 0.361 AC: 5519 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2551 AN: 5176

South Asian (SAS) AF: 0.342 AC: 1647 AN: 4810

European-Finnish (FIN) AF: 0.158 AC: 1665 AN: 10568

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16804 AN: 67986

Other (OTH) AF: 0.261 AC: 551 AN: 2114

Alfa AF: 0.249 Hom.: 2655

Bravo AF: 0.267

Asia WGS AF: 0.394 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	11
DANN	Benign	0.46
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17095967; hg19: chr14-59725803;