rs74579395

Variant names:

• chr6-39861048-C-T
• rs74579395
• ENST00000405961.3:c.289C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000405961.3(DAAM2):​c.289C>T​(p.Gln97*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000725 in 1,560,426 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (7 hom.)
• Consequence: DAAM2 ENST00000405961.3 stop_gained
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.128
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 6-39861048-C-T is Benign according to our data. Variant chr6-39861048-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3770972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000405961.3. 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.258+31C>T		intron	N/A	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.258+31C>T		intron	N/A	NP_056160.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	ENST00000405961.3	TSL:1	c.289C>T	p.Gln97*	stop_gained	Exon 3 of 3	ENSP00000384637.3	F2Z2Q2
	DAAM2	ENST00000274867.9	TSL:1 MANE Select	c.258+31C>T		intron	N/A	ENSP00000274867.4	Q86T65-3
	DAAM2	ENST00000538976.5	TSL:1	c.258+31C>T		intron	N/A	ENSP00000437808.1	Q86T65-4

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 575 AN: 152200 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

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: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000966 AC: 199 AN: 205962 AF XY: 0.000806

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.000742

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000111

Gnomad OTH exome AF: 0.000189

GnomAD4 exome AF: 0.000394 AC: 555 AN: 1408108 Hom.: 7 Cov.: 24 AF XY: 0.000351 AC XY: 246 AN XY: 699954

African (AFR) AF: 0.0143 AC: 462 AN: 32372

American (AMR) AF: 0.000757 AC: 31 AN: 40940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25400

East Asian (EAS) AF: 0.00 AC: 0 AN: 38408

South Asian (SAS) AF: 0.0000245 AC: 2 AN: 81564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.0000121 AC: 13 AN: 1073044

Other (OTH) AF: 0.000801 AC: 47 AN: 58698

GnomAD4 genome AF: 0.00379 AC: 577 AN: 152318 Hom.: 3 Cov.: 32 AF XY: 0.00376 AC XY: 280 AN XY: 74480

African (AFR) AF: 0.0134 AC: 558 AN: 41566

American (AMR) AF: 0.000784 AC: 12 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00495 Hom.: 3

Bravo AF: 0.00452

ESP6500AA AF: 0.0124 AC: 49

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000963 AC: 116

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely 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_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.3
DANN	Benign	0.97
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.077	N
PhyloP100		-0.13
Vest4		0.27
GERP RS		2.0
Mutation Taster		=181/19	polymorphism

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: rs74579395; hg19: chr6-39828824;