chr10-95961859-G-T

Variant names:

• chr10-95961859-G-T
• rs41291590
• NM_001349008.3:c.1140G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001349008.3(CC2D2B):​c.1140G>T​(p.Arg380Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000926 in 1,079,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict 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. R380R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: CC2D2B NM_001349008.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 0 publications found

Genes affected

CC2D2B (HGNC:31666): (coiled-coil and C2 domain containing 2B) Predicted to be involved in non-motile cilium assembly and protein localization to ciliary transition zone. Predicted to be active in ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

ENTPD1-AS1 (HGNC:45203): (ENTPD1 antisense RNA 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21521133).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349008.3. 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
	CC2D2B	NM_001349008.3	MANE Select	c.1140G>T	p.Arg380Ser	missense	Exon 12 of 35	NP_001335937.1	Q6DHV5-5
	ENTPD1-AS1	NR_038444.1		n.297-85199C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D2B	ENST00000646931.3	MANE Select	c.1140G>T	p.Arg380Ser	missense	Exon 12 of 35	ENSP00000496666.2	Q6DHV5-5
	CC2D2B	ENST00000636965.1	TSL:5	c.1116G>T	p.Arg372Ser	missense	Exon 11 of 25	ENSP00000490447.1	A0A5S8K7B6
	CC2D2B	ENST00000472454.6	TSL:5	n.*226G>T		non_coding_transcript_exon	Exon 4 of 12	ENSP00000491867.1	A0A1W2PQR2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.26e-7 AC: 1 AN: 1079336 Hom.: 0 Cov.: 29 AF XY: 0.00000196 AC XY: 1 AN XY: 509534

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22940

American (AMR) AF: 0.00 AC: 0 AN: 8410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14366

East Asian (EAS) AF: 0.00 AC: 0 AN: 26494

South Asian (SAS) AF: 0.00 AC: 0 AN: 19486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2904

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 919580

Other (OTH) AF: 0.00 AC: 0 AN: 43634

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	16
DANN	Benign	0.80
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.22	T
PhyloP100		-0.18
GERP RS		2.7
Varity_R		0.14
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs41291590; hg19: chr10-97721616;