7-16308637-AAACAACAAC-AAAC

Variant names:

• chr7-16308637-AAACAAC-A
• rs142647500
• NM_001101426.4:c.685-16_685-11delGTTGTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001101426.4(CRPPA):​c.685-16_685-11delGTTGTT variant causes a intron 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRPPA NM_001101426.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.23
• Publications: 2 publications found

Genes affected

CRPPA (HGNC:37276): (CDP-L-ribitol pyrophosphorylase A) This gene encodes a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein. Mutations in this gene are the cause of Walker-Warburg syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

CRPPA Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• myopathy caused by variation in CRPPA

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2U

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy without intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 7-16308637-AAACAAC-A is Benign according to our data. Variant chr7-16308637-AAACAAC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3758602.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101426.4. 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
	CRPPA	NM_001101426.4	MANE Select	c.685-16_685-11delGTTGTT		intron	N/A	NP_001094896.1	A4D126-1
	CRPPA	NM_001368197.1		c.685-7177_685-7172delGTTGTT		intron	N/A	NP_001355126.1
	CRPPA	NM_001101417.4		c.535-16_535-11delGTTGTT		intron	N/A	NP_001094887.1	A0A140VJM1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRPPA	ENST00000407010.7	TSL:5 MANE Select	c.685-16_685-11delGTTGTT		intron	N/A	ENSP00000385478.2	A4D126-1
	CRPPA	ENST00000399310.3	TSL:1	c.535-16_535-11delGTTGTT		intron	N/A	ENSP00000382249.3	A4D126-2
	CRPPA	ENST00000856526.1		c.685-16_685-11delGTTGTT		intron	N/A	ENSP00000526585.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1254068 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 633188

African (AFR) AF: 0.00 AC: 0 AN: 28500

American (AMR) AF: 0.00 AC: 0 AN: 42078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24608

East Asian (EAS) AF: 0.00 AC: 0 AN: 37896

South Asian (SAS) AF: 0.00 AC: 0 AN: 79498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5420

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 930182

Other (OTH) AF: 0.00 AC: 0 AN: 53140

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7;C5190987:Autosomal recessive limb-girdle muscular dystrophy type 2U (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

Splicing

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

Other links and lift over

dbSNP: rs142647500; hg19: chr7-16348262;