chr6-39832238-A-G

Variant names:

• chr6-39832238-A-G
• rs6937133
• NM_001201427.2:c.-56-24009A>G

Variant summary

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

The NM_001201427.2(DAAM2):​c.-56-24009A>G 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 151,798 control chromosomes in the GnomAD database, including 5,019 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 (5019 hom., cov: 31)
• Consequence: DAAM2 NM_001201427.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 4 publications found

Genes affected

DAAM2 (HGNC:18143): (dishevelled associated activator of morphogenesis 2) Predicted to enable actin binding activity and small GTPase binding activity. Predicted to be involved in nervous system development and regulation of Wnt signaling pathway. Predicted to act upstream of or within determination of left/right symmetry. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

DAAM2 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 24

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• idiopathic multidrug-resistant nephrotic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201427.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	NM_001201427.2	MANE Select	c.-56-24009A>G		intron	N/A	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.-56-24009A>G		intron	N/A	NP_056160.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	ENST00000274867.9	TSL:1 MANE Select	c.-56-24009A>G		intron	N/A	ENSP00000274867.4	Q86T65-3
	DAAM2	ENST00000538976.5	TSL:1	c.-56-24009A>G		intron	N/A	ENSP00000437808.1	Q86T65-4
	DAAM2	ENST00000475489.5	TSL:1	n.71-24009A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38259 AN: 151680 Hom.: 5013 Cov.: 31

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.252 AC: 38284 AN: 151798 Hom.: 5019 Cov.: 31 AF XY: 0.253 AC XY: 18727 AN XY: 74166

African (AFR) AF: 0.284 AC: 11736 AN: 41304

American (AMR) AF: 0.226 AC: 3456 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3466

East Asian (EAS) AF: 0.372 AC: 1916 AN: 5154

South Asian (SAS) AF: 0.380 AC: 1828 AN: 4814

European-Finnish (FIN) AF: 0.183 AC: 1934 AN: 10578

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15576 AN: 67900

Other (OTH) AF: 0.228 AC: 479 AN: 2104

Alfa AF: 0.233 Hom.: 7137

Bravo AF: 0.256

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.13
DANN	Benign	0.42
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: rs6937133; hg19: chr6-39800014;