rs2790457

Variant names:

• chr10-28567890-G-A
• rs2790457
• NM_016628.5:c.275-15509G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-28567890-G-A
• chr10-28567890-G-C

Variant summary

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

The NM_016628.5(WAC):​c.275-15509G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,884 control chromosomes in the GnomAD database, including 10,050 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 0.35 (10050 hom., cov: 31)
• Consequence: WAC NM_016628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 10 publications found

Genes affected

WAC (HGNC:17327): (WW domain containing adaptor with coiled-coil) The protein encoded by this gene contains a WW domain, which is a protein module found in a wide range of signaling proteins. This domain mediates protein-protein interactions and binds proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. This gene product shares 94% sequence identity with the WAC protein in mouse, however, its exact function is not known. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

WAC Gene-Disease associations (from GenCC):

• DeSanto-Shinawi syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• DeSanto-Shinawi syndrome due to WAC point mutation

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAC	NM_016628.5	c.275-15509G>A		intron_variant	Intron 3 of 13	ENST00000354911.9	NP_057712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WAC	ENST00000354911.9	c.275-15509G>A		intron_variant	Intron 3 of 13	1	NM_016628.5	ENSP00000346986.4
WAC	ENST00000428935.6	c.140-15509G>A		intron_variant	Intron 3 of 7	2		ENSP00000399706.3
WAC	ENST00000651885.1	c.293-15509G>A		intron_variant	Intron 3 of 4			ENSP00000498678.1
WAC	ENST00000651598.1	c.140-15509G>A		intron_variant	Intron 3 of 5			ENSP00000498480.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53168 AN: 151766 Hom.: 10044 Cov.: 31

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.350 AC: 53189 AN: 151884 Hom.: 10050 Cov.: 31 AF XY: 0.354 AC XY: 26252 AN XY: 74210

African (AFR) AF: 0.443 AC: 18318 AN: 41362

American (AMR) AF: 0.432 AC: 6591 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3470

East Asian (EAS) AF: 0.540 AC: 2771 AN: 5130

South Asian (SAS) AF: 0.471 AC: 2265 AN: 4812

European-Finnish (FIN) AF: 0.241 AC: 2549 AN: 10566

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18381 AN: 67966

Other (OTH) AF: 0.367 AC: 773 AN: 2106

Alfa AF: 0.315 Hom.: 1260

Bravo AF: 0.367

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.76
PhyloP100		0.36
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: rs2790457; hg19: chr10-28856819;