6-130869572-AC-GT

Variant names:

• chr6-130869572-AC-GT
• NM_001431.4:c.2597_2598delGTinsAC
• EPB41L2 p.Cys866Tyr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001431.4(EPB41L2):​c.2597_2598delGTinsAC​(p.Cys866Tyr) variant causes a missense change involving the alteration of a 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. C866F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EPB41L2 NM_001431.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.46
• Publications: 0 publications found

Genes affected

EPB41L2 (HGNC:3379): (erythrocyte membrane protein band 4.1 like 2) Predicted to enable PH domain binding activity; cytoskeletal protein binding activity; and structural molecule activity. Involved in positive regulation of protein localization to cell cortex. Located in cell junction; nucleoplasm; and plasma membrane. Colocalizes with COP9 signalosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001431.4. 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
	EPB41L2	NM_001431.4	MANE Select	c.2597_2598delGTinsAC	p.Cys866Tyr	missense	N/A	NP_001422.1	O43491-1
	EPB41L2	NM_001350299.2		c.2753_2754delGTinsAC	p.Cys918Tyr	missense	N/A	NP_001337228.1	A0A994J5B1
	EPB41L2	NM_001350301.2		c.2753_2754delGTinsAC	p.Cys918Tyr	missense	N/A	NP_001337230.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPB41L2	ENST00000337057.8	TSL:1 MANE Select	c.2597_2598delGTinsAC	p.Cys866Tyr	missense	N/A	ENSP00000338481.3	O43491-1
	EPB41L2	ENST00000524581.5	TSL:1	c.731_732delGTinsAC	p.Cys244Tyr	missense	N/A	ENSP00000437207.1	Q6R5J7
	EPB41L2	ENST00000528282.5	TSL:1	c.1834-1992_1834-1991delGTinsAC		intron	N/A	ENSP00000434308.1	O43491-3

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		8.5

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: chr6-131190712;