rs372338719

Variant names:

• chr10-133279872-C-T
• rs372338719
• NM_006659.4:c.2603G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-133279872-C-T
• chr10-133279872-C-A

Variant summary

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

The NM_006659.4(TUBGCP2):​c.2603G>A​(p.Arg868His) variant causes a missense change. The variant allele was found at a frequency of 0.0000522 in 1,608,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: TUBGCP2 NM_006659.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79
• Publications: 1 publications found

Genes affected

TUBGCP2 (HGNC:18599): (tubulin gamma complex component 2) Predicted to enable gamma-tubulin binding activity. Predicted to contribute to microtubule minus-end binding activity. Involved in brain development and neuron migration. Located in centrosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TUBGCP2 Gene-Disease associations (from GenCC):

• pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

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=0.25073168).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006659.4. 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
	TUBGCP2	NM_006659.4	MANE Select	c.2603G>A	p.Arg868His	missense	Exon 18 of 18	NP_006650.1	Q9BSJ2-1
	TUBGCP2	NM_001256617.2		c.2687G>A	p.Arg896His	missense	Exon 19 of 19	NP_001243546.1	Q9BSJ2-4
	TUBGCP2	NM_001256618.2		c.2213G>A	p.Arg738His	missense	Exon 17 of 17	NP_001243547.1	Q9BSJ2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBGCP2	ENST00000252936.8	TSL:2 MANE Select	c.2603G>A	p.Arg868His	missense	Exon 18 of 18	ENSP00000252936.3	Q9BSJ2-1
	TUBGCP2	ENST00000543663.6	TSL:1	c.2687G>A	p.Arg896His	missense	Exon 19 of 19	ENSP00000446093.1	Q9BSJ2-4
	TUBGCP2	ENST00000682161.1		c.2672G>A	p.Arg891His	missense	Exon 17 of 17	ENSP00000507509.1	A0A804HJH7

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000208 AC: 5 AN: 240856 AF XY: 0.0000152

Gnomad AFR exome AF: 0.0000660

Gnomad AMR exome AF: 0.0000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000277

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000549 AC: 80 AN: 1456500 Hom.: 0 Cov.: 31 AF XY: 0.0000483 AC XY: 35 AN XY: 724370

African (AFR) AF: 0.0000300 AC: 1 AN: 33316

American (AMR) AF: 0.0000227 AC: 1 AN: 43976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39460

South Asian (SAS) AF: 0.00 AC: 0 AN: 85542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000703 AC: 78 AN: 1110178

Other (OTH) AF: 0.00 AC: 0 AN: 60196

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152218 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74360

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.20
Sift	Benign	0.088	T
Sift4G	Benign	0.066	T
Polyphen		1.0	D
Vest4		0.39
MVP		0.53
MPC		1.1
ClinPred		0.83	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.50
Mutation Taster		=42/58	disease causing

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: rs372338719; hg19: chr10-135093376;