rs886037662

Variant names:

• chr9-95921216-TCAAA-T
• rs886037662
• NM_020207.7:c.1203_1206delAACA

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_020207.7(ERCC6L2):​c.1203_1206delAACA​(p.Thr402CysfsTer2) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. Q401Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ERCC6L2 NM_020207.7 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.38
• Publications: 1 publications found

Genes affected

ERCC6L2 (HGNC:26922): (ERCC excision repair 6 like 2) This gene encodes a member of the Snf2 family of helicase-like proteins. The encoded protein may play a role in DNA repair and mitochondrial function. Mutations in this gene have been associated with bone marrow failure syndrome 2. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Apr 2014]

ERCC6L2 Gene-Disease associations (from GenCC):

• pancytopenia-developmental delay syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-95921216-TCAAA-T is Pathogenic according to our data. Variant chr9-95921216-TCAAA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 125450.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020207.7. 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
	ERCC6L2	NM_020207.7	MANE Select	c.1203_1206delAACA	p.Thr402CysfsTer2	frameshift	Exon 7 of 19	NP_064592.3	Q5T890-1
	ERCC6L2	NM_001375291.1		c.1203_1206delAACA	p.Thr402CysfsTer2	frameshift	Exon 7 of 19	NP_001362220.1
	ERCC6L2	NM_001375292.1		c.1203_1206delAACA	p.Thr402CysfsTer2	frameshift	Exon 7 of 19	NP_001362221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC6L2	ENST00000653738.2	MANE Select	c.1203_1206delAACA	p.Thr402CysfsTer2	frameshift	Exon 7 of 19	ENSP00000499221.2	Q5T890-1
	ERCC6L2	ENST00000288985.13	TSL:1	c.1203_1206delAACA	p.Thr402CysfsTer2	frameshift	Exon 7 of 14	ENSP00000288985.8	A0A5F9UKL4
	ERCC6L2	ENST00000456993.7	TSL:1	n.*385_*388delAACA		non_coding_transcript_exon	Exon 6 of 18	ENSP00000409751.2	F2Z2R4

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Pancytopenia-developmental delay syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.4
Mutation Taster		=27/173	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

dbSNP: rs886037662;

hg19: chr9-98683498;