5-66025482-TCG-CTC

Variant names:

• chr5-66025482-TCG-CTC
• NM_001253697.2:c.820_822delTCGinsCTC
• ERBIN p.Ser274Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001253697.2(ERBIN):​c.820_822delTCGinsCTC​(p.Ser274Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. S274S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERBIN NM_001253697.2 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 0 publications found

Genes affected

ERBIN (HGNC:15842): (erbb2 interacting protein) This gene is a member of the leucine-rich repeat and PDZ domain (LAP) family. The encoded protein contains 17 leucine-rich repeats and one PDZ domain. It binds to the unphosphorylated form of the ERBB2 protein and regulates ERBB2 function and localization. It has also been shown to affect the Ras signaling pathway by disrupting Ras-Raf interaction. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ERBIN Gene-Disease associations (from GenCC):

• autosomal dominant combined immunodeficiency due to ERBIN deficiency

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253697.2. 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
	ERBIN	NM_001253697.2	MANE Select	c.820_822delTCGinsCTC	p.Ser274Leu	missense splice_region	N/A	NP_001240626.1	Q96RT1-1
	ERBIN	NM_001253699.2		c.820_822delTCGinsCTC	p.Ser274Leu	missense splice_region	N/A	NP_001240628.1	Q96RT1-8
	ERBIN	NM_018695.4		c.820_822delTCGinsCTC	p.Ser274Leu	missense splice_region	N/A	NP_061165.1	Q96RT1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERBIN	ENST00000284037.10	TSL:1 MANE Select	c.820_822delTCGinsCTC	p.Ser274Leu	missense splice_region	N/A	ENSP00000284037.4	Q96RT1-1
	ERBIN	ENST00000506030.6	TSL:1	c.820_822delTCGinsCTC	p.Ser274Leu	missense splice_region	N/A	ENSP00000426632.1	Q96RT1-8
	ERBIN	ENST00000380943.6	TSL:1	c.820_822delTCGinsCTC	p.Ser274Leu	missense splice_region	N/A	ENSP00000370330.2	Q96RT1-2

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
PhyloP100		2.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-65321310;