rs1554815871

Variant names:

• chr10-53809487-TTCC-T
• rs1554815871
• ENST00000395445.6:c.4554_4556delGGA

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PM4_Supporting BP6_Moderate

The NM_001142769.3(PCDH15):​c.4575_4577delGGA​(p.Glu1526del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCDH15 NM_001142769.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.75
• Publications: 0 publications found

Genes affected

PCDH15 (HGNC:14674): (protocadherin related 15) This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. It plays an essential role in maintenance of normal retinal and cochlear function. Mutations in this gene result in hearing loss and Usher Syndrome Type IF (USH1F). Extensive alternative splicing resulting in multiple isoforms has been observed in the mouse ortholog. Similar alternatively spliced transcripts are inferred to occur in human, and additional variants are likely to occur. [provided by RefSeq, Dec 2008]

PCDH15 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 23

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• Usher syndrome type 1

  Inheritance: AR, Unknown Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Usher syndrome type 1F

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001142769.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 10-53809487-TTCC-T is Benign according to our data. Variant chr10-53809487-TTCC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 517368.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142769.3. 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
	PCDH15	NM_001384140.1	MANE Select	c.4671+1066_4671+1068delGGA		intron	N/A	NP_001371069.1	Q96QU1-7
	PCDH15	NM_001142769.3		c.4575_4577delGGA	p.Glu1526del	disruptive_inframe_deletion	Exon 37 of 37	NP_001136241.1	A0A087WZN9
	PCDH15	NM_001354411.2		c.4554_4556delGGA	p.Glu1519del	disruptive_inframe_deletion	Exon 35 of 35	NP_001341340.1	Q96QU1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH15	ENST00000395445.6	TSL:1	c.4554_4556delGGA	p.Glu1519del	disruptive_inframe_deletion	Exon 35 of 35	ENSP00000378832.2	Q96QU1-4
	PCDH15	ENST00000644397.2	MANE Select	c.4671+1066_4671+1068delGGA		intron	N/A	ENSP00000495195.1	Q96QU1-7
	PCDH15	ENST00000616114.4	TSL:1	c.4476+1066_4476+1068delGGA		intron	N/A	ENSP00000483745.1	Q96QU1-6

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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8
Mutation Taster		=65/35	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: rs1554815871; hg19: chr10-55569247;