rs2146009

Variant names:

• chr14-59208145-T-A
• rs2146009
• NM_001270520.2:c.-38+19377T>A

Your query was ambiguous. Multiple possible variants found:

• chr14-59208145-T-A
• chr14-59208145-T-C

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.7).
• 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 rank	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.-38+19377T>A		intron_variant	Intron 1 of 24	ENST00000360909.8	NP_001257449.1
DAAM1	XM_005267430.3	c.-38+19377T>A		intron_variant	Intron 1 of 25		XP_005267487.1
DAAM1	XM_005267431.2	c.-38+19231T>A		intron_variant	Intron 1 of 25		XP_005267488.1
DAAM1	XM_047431135.1	c.-38+19231T>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.-38+19377T>A		intron_variant	Intron 1 of 24	1	NM_001270520.2	ENSP00000354162.3
DAAM1	ENST00000556596.1	n.123+19377T>A		intron_variant	Intron 1 of 1	1
DAAM1	ENST00000556135.1	c.-38+19377T>A		intron_variant	Intron 1 of 2	3		ENSP00000450498.1

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

African (AFR) AF: 0.202 AC: 8378 AN: 41500

American (AMR) AF: 0.379 AC: 5785 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 867 AN: 3470

East Asian (EAS) AF: 0.487 AC: 2520 AN: 5172

South Asian (SAS) AF: 0.350 AC: 1687 AN: 4820

European-Finnish (FIN) AF: 0.159 AC: 1685 AN: 10590

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17042 AN: 67974

Other (OTH) AF: 0.271 AC: 571 AN: 2108

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
PhyloP100		0.47
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: rs2146009; hg19: chr14-59674863;