6-39816358-T-C

Variant names:

• chr6-39816358-T-C
• rs1318002
• NM_001201427.2:c.-57+23893T>C

Variant summary

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

The NM_001201427.2(DAAM2):​c.-57+23893T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,046 control chromosomes in the GnomAD database, including 22,575 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 0.54 (22575 hom., cov: 32)
• Consequence: DAAM2 NM_001201427.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 2 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)

ENSG00000308921 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	NM_001201427.2	MANE Select	c.-57+23893T>C		intron	N/A	NP_001188356.1
	DAAM2	NM_015345.4		c.-57+23215T>C		intron	N/A	NP_056160.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	ENST00000274867.9	TSL:1 MANE Select	c.-57+23893T>C		intron	N/A	ENSP00000274867.4
	DAAM2	ENST00000538976.5	TSL:1	c.-57+23215T>C		intron	N/A	ENSP00000437808.1
	DAAM2	ENST00000475489.5	TSL:1	n.70+23893T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82451 AN: 151928 Hom.: 22556 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.543 AC: 82514 AN: 152046 Hom.: 22575 Cov.: 32 AF XY: 0.546 AC XY: 40552 AN XY: 74326

African (AFR) AF: 0.545 AC: 22590 AN: 41434

American (AMR) AF: 0.582 AC: 8901 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1890 AN: 3470

East Asian (EAS) AF: 0.625 AC: 3232 AN: 5170

South Asian (SAS) AF: 0.546 AC: 2634 AN: 4822

European-Finnish (FIN) AF: 0.547 AC: 5785 AN: 10568

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35598 AN: 67984

Other (OTH) AF: 0.535 AC: 1127 AN: 2106

Alfa AF: 0.531 Hom.: 60747

Bravo AF: 0.544

Asia WGS AF: 0.518 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		0.13
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: rs1318002; hg19: chr6-39784134;