2-96761060-CTGGCGGCGCCGGTGCTGCTGGTGCTGCTGTGGGCGCTGGGGGCCCGGGGCCAGGGCAGCCCCCAGCAGGGCACGATCGTGGGCA-C

Position:

• chr2-96761060-CTGGCGGCGCCGGTGCTGCTGGTGCTGCTGTGGGCGCTGGGGGCCCGGGGCCAGGGCAGCCCCCAGCAGGGCACGATCGTGGGCA-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_020184.4(CNNM4):​c.64_147del​(p.Ala22_Met49del) variant causes a 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CNNM4 NM_020184.4 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.25

Genes affected

CNNM4 (HGNC:105): (cyclin and CBS domain divalent metal cation transport mediator 4) This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play a role in metal ion transport. Mutations in this gene are associated with Jalili syndrome which consists of cone-rod dystrophy and amelogenesis imperfecta. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_020184.4.
• PP5: Variant 2-96761060-CTGGCGGCGCCGGTGCTGCTGGTGCTGCTGTGGGCGCTGGGGGCCCGGGGCCAGGGCAGCCCCCAGCAGGGCACGATCGTGGGCA-C is Pathogenic according to our data. Variant chr2-96761060-CTGGCGGCGCCGGTGCTGCTGGTGCTGCTGTGGGCGCTGGGGGCCCGGGGCCAGGGCAGCCCCCAGCAGGGCACGATCGTGGGCA-C is described in ClinVar as [Pathogenic]. Clinvar id is 2853.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-96761060-CTGGCGGCGCCGGTGCTGCTGGTGCTGCTGTGGGCGCTGGGGGCCCGGGGCCAGGGCAGCCCCCAGCAGGGCACGATCGTGGGCA-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNNM4	NM_020184.4	c.64_147del	p.Ala22_Met49del	inframe_deletion	1/7	ENST00000377075.3	NP_064569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNNM4	ENST00000377075.3	c.64_147del	p.Ala22_Met49del	inframe_deletion	1/7	1	NM_020184.4	ENSP00000366275	P1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Jalili syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-97426797;