2-174812294-C-A

Variant names:

• chr2-174812294-C-A
• rs12613075
• NM_001822.7:c.886+15G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001822.7(CHN1):​c.886+15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHN1 NM_001822.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 7 publications found

Genes affected

CHN1 (HGNC:1943): (chimerin 1) This gene encodes GTPase-activating protein for ras-related p21-rac and a phorbol ester receptor. It is predominantly expressed in neurons, and plays an important role in neuronal signal-transduction mechanisms. Mutations in this gene are associated with Duane's retraction syndrome 2 (DURS2). Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

CHN1 Gene-Disease associations (from GenCC):

• Duane retraction syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Duane retraction syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000236449 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001822.7. 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
	CHN1	NM_001822.7	MANE Select	c.886+15G>T		intron	N/A	NP_001813.1	P15882-1
	CHN1	NM_001371514.1		c.937+15G>T		intron	N/A	NP_001358443.1
	CHN1	NM_001371513.1		c.886+15G>T		intron	N/A	NP_001358442.1	P15882-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN1	ENST00000409900.9	TSL:1 MANE Select	c.886+15G>T		intron	N/A	ENSP00000386741.4	P15882-1
	CHN1	ENST00000295497.13	TSL:1	c.511+15G>T		intron	N/A	ENSP00000295497.7	P15882-2
	CHN1	ENST00000488080.6	TSL:1	n.529+15G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.36
PhyloP100		0.035

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12613075; hg19: chr2-175677022;