chr4-15567395-G-T

Variant names:

• chr4-15567395-G-T
• rs73125627
• NM_001378615.1:c.3201G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001378615.1(CC2D2A):​c.3201G>T​(p.Ser1067Ser) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. S1067S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CC2D2A NM_001378615.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.60
• Publications: 21 publications found

Genes affected

CC2D2A (HGNC:29253): (coiled-coil and C2 domain containing 2A) This gene encodes a coiled-coil and calcium binding domain protein that appears to play a critical role in cilia formation. Mutations in this gene cause Meckel syndrome type 6, as well as Joubert syndrome type 9. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

CC2D2A Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Joubert syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• retinitis pigmentosa 93

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• COACH syndrome 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with oculorenal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124900671 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-5.6 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378615.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D2A	NM_001378615.1	MANE Select	c.3201G>T	p.Ser1067Ser	synonymous	Exon 25 of 37	NP_001365544.1
	CC2D2A	NM_001080522.2		c.3201G>T	p.Ser1067Ser	synonymous	Exon 26 of 38	NP_001073991.2
	CC2D2A	NM_001378617.1		c.3054G>T	p.Ser1018Ser	synonymous	Exon 23 of 35	NP_001365546.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D2A	ENST00000424120.6	TSL:5 MANE Select	c.3201G>T	p.Ser1067Ser	synonymous	Exon 25 of 37	ENSP00000403465.1
	CC2D2A	ENST00000503292.6	TSL:1	c.3201G>T	p.Ser1067Ser	synonymous	Exon 26 of 38	ENSP00000421809.1
	CC2D2A	ENST00000634028.2	TSL:1	n.3054G>T		non_coding_transcript_exon	Exon 22 of 34	ENSP00000488669.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2760

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.032
DANN	Benign	0.28
PhyloP100		-5.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73125627; hg19: chr4-15569018;