rs182451824

Variant names:

• chr10-28533924-G-A
• rs182451824
• NM_016628.5:c.42-74G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-28533924-G-A
• chr10-28533924-G-C
• chr10-28533924-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_016628.5(WAC):​c.42-74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,559,918 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (8 hom., cov: 32)
  • Exomes 𝑓: 0.013 (167 hom.)
• Consequence: WAC NM_016628.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.185
• Publications: 1 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: Labcorp Genetics (formerly Invitae), Illumina, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-28533924-G-A is Benign according to our data. Variant chr10-28533924-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1197674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1391 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016628.5. 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
	WAC	NM_016628.5	MANE Select	c.42-74G>A		intron	N/A	NP_057712.2
	WAC	NM_100264.3		c.-94-74G>A		intron	N/A	NP_567822.1	Q9BTA9-2
	WAC	NM_100486.4		c.42-74G>A		intron	N/A	NP_567823.1	Q9BTA9-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WAC	ENST00000354911.9	TSL:1 MANE Select	c.42-74G>A		intron	N/A	ENSP00000346986.4	Q9BTA9-1
	WAC	ENST00000375664.8	TSL:1	c.-94-74G>A		intron	N/A	ENSP00000364816.3	Q9BTA9-2
	WAC	ENST00000428935.6	TSL:2	c.-94-74G>A		intron	N/A	ENSP00000399706.3	A0A0A0MSR1

Frequencies

GnomAD3 genomes AF: 0.00915 AC: 1392 AN: 152166 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.0127 AC: 17879 AN: 1407642 Hom.: 167 Cov.: 25 AF XY: 0.0124 AC XY: 8734 AN XY: 702208

African (AFR) AF: 0.00257 AC: 79 AN: 30698

American (AMR) AF: 0.00754 AC: 318 AN: 42148

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 462 AN: 25052

East Asian (EAS) AF: 0.00 AC: 0 AN: 37640

South Asian (SAS) AF: 0.00553 AC: 467 AN: 84402

European-Finnish (FIN) AF: 0.00289 AC: 150 AN: 51948

Middle Eastern (MID) AF: 0.00705 AC: 29 AN: 4112

European-Non Finnish (NFE) AF: 0.0146 AC: 15635 AN: 1073480

Other (OTH) AF: 0.0127 AC: 739 AN: 58162

GnomAD4 genome AF: 0.00913 AC: 1391 AN: 152276 Hom.: 8 Cov.: 32 AF XY: 0.00881 AC XY: 656 AN XY: 74466

African (AFR) AF: 0.00298 AC: 124 AN: 41572

American (AMR) AF: 0.0109 AC: 167 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5154

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4832

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0145 AC: 986 AN: 67998

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00617 Hom.: 3

Bravo AF: 0.00992

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.77
PhyloP100		-0.18
PromoterAI		-0.099	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	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: rs182451824; hg19: chr10-28822853;