chr10-28569649-C-G

Variant names:

• chr10-28569649-C-G
• rs332136
• NM_016628.5:c.275-13750C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016628.5(WAC):​c.275-13750C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: WAC NM_016628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 5 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, Orphanet, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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.275-13750C>G		intron	N/A	NP_057712.2
	WAC	NM_100264.3		c.140-13750C>G		intron	N/A	NP_567822.1	Q9BTA9-2
	WAC	NM_100486.4		c.275-13750C>G		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.275-13750C>G		intron	N/A	ENSP00000346986.4	Q9BTA9-1
	WAC	ENST00000375664.8	TSL:1	c.140-13750C>G		intron	N/A	ENSP00000364816.3	Q9BTA9-2
	WAC	ENST00000428935.6	TSL:2	c.140-13750C>G		intron	N/A	ENSP00000399706.3	A0A0A0MSR1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.44
PhyloP100		-0.25

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: rs332136; hg19: chr10-28858578;