rs73734938

Variant names:

• chr6-39867500-T-C
• rs73734938
• NM_001201427.2:c.429-10T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001201427.2(DAAM2):​c.429-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,612,252 control chromosomes in the GnomAD database, including 215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (114 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (101 hom.)
• Consequence: DAAM2 NM_001201427.2 intron
• Scores: Splicing: ADA: 0.001574
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.708
• Publications: 0 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-AS1 (HGNC:40830): (DAAM2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-39867500-T-C is Benign according to our data. Variant chr6-39867500-T-C is described in ClinVar as Benign. ClinVar VariationId is 783753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0704 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.429-10T>C		intron	N/A	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.429-10T>C		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.429-10T>C		intron	N/A	ENSP00000274867.4	Q86T65-3
	DAAM2	ENST00000538976.5	TSL:1	c.429-10T>C		intron	N/A	ENSP00000437808.1	Q86T65-4
	DAAM2	ENST00000491083.2	TSL:1	n.575-10T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3207 AN: 152198 Hom.: 115 Cov.: 33

Gnomad AFR AF: 0.0728

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00561 AC: 1389 AN: 247386 AF XY: 0.00430

Gnomad AFR exome AF: 0.0794

Gnomad AMR exome AF: 0.00362

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000189

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00212 AC: 3095 AN: 1459936 Hom.: 101 Cov.: 30 AF XY: 0.00187 AC XY: 1359 AN XY: 725938

African (AFR) AF: 0.0744 AC: 2490 AN: 33456

American (AMR) AF: 0.00416 AC: 186 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5758

European-Non Finnish (NFE) AF: 0.000138 AC: 153 AN: 1110338

Other (OTH) AF: 0.00403 AC: 243 AN: 60320

GnomAD4 genome AF: 0.0211 AC: 3207 AN: 152316 Hom.: 114 Cov.: 33 AF XY: 0.0206 AC XY: 1531 AN XY: 74484

African (AFR) AF: 0.0725 AC: 3014 AN: 41554

American (AMR) AF: 0.00915 AC: 140 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68028

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.0138 Hom.: 32

Bravo AF: 0.0246

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.9
DANN	Benign	0.76
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0016
dbscSNV1_RF	Benign	0.11
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: rs73734938; hg19: chr6-39835276;