rs2395730

Variant names:

• chr6-39816589-C-A
• rs2395730
• NM_001201427.2:c.-57+24124C>A

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+24124C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,064 control chromosomes in the GnomAD database, including 25,999 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 0.58 (25999 hom., cov: 32)
• Consequence: DAAM2 NM_001201427.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM2	NM_001201427.2	c.-57+24124C>A		intron_variant	Intron 1 of 24	ENST00000274867.9	NP_001188356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9	c.-57+24124C>A		intron_variant	Intron 1 of 24	1	NM_001201427.2	ENSP00000274867.4

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88529 AN: 151946 Hom.: 25980 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.583 AC: 88597 AN: 152064 Hom.: 25999 Cov.: 32 AF XY: 0.588 AC XY: 43723 AN XY: 74300

African (AFR) AF: 0.582 AC: 24153 AN: 41476

American (AMR) AF: 0.608 AC: 9288 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2031 AN: 3472

East Asian (EAS) AF: 0.681 AC: 3518 AN: 5168

South Asian (SAS) AF: 0.708 AC: 3409 AN: 4812

European-Finnish (FIN) AF: 0.584 AC: 6176 AN: 10580

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38045 AN: 67968

Other (OTH) AF: 0.573 AC: 1207 AN: 2108

Alfa AF: 0.573 Hom.: 81456

Bravo AF: 0.581

Asia WGS AF: 0.647 AC: 2251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.80
DANN	Benign	0.63
PhyloP100		0.047
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: rs2395730; hg19: chr6-39784365;