rs746063573

Variant names:

• chr7-93197553-C-A
• rs746063573
• NM_001039372.4:c.1070G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-93197553-C-A
• chr7-93197553-C-G
• chr7-93197553-C-T

Variant summary

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

The NM_001039372.4(HEPACAM2):​c.1070G>T​(p.Gly357Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,444,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: HEPACAM2 NM_001039372.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 1 publications found

Genes affected

HEPACAM2 (HGNC:27364): (HEPACAM family member 2) This gene encodes a protein related to the immunoglobulin superfamily that plays a role in mitosis. Knockdown of this gene results in prometaphase arrest, abnormal nuclear morphology and apoptosis. Poly(ADP-ribosylation) of the encoded protein promotes its translocation to centrosomes, which may stimulate centrosome maturation. A chromosomal deletion including this gene may be associated with myeloid leukemia and myelodysplastic syndrome in human patients. [provided by RefSeq, Oct 2016]

HEPACAM2 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039372.4. 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
	HEPACAM2	NM_001039372.4	MANE Select	c.1070G>T	p.Gly357Val	missense	Exon 5 of 10	NP_001034461.1	A8MVW5-1
	HEPACAM2	NM_001288804.3		c.1139G>T	p.Gly380Val	missense	Exon 6 of 11	NP_001275733.1	A8MVW5-3
	HEPACAM2	NM_001288810.3		c.1034G>T	p.Gly345Val	missense	Exon 4 of 8	NP_001275739.1	C9JN07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEPACAM2	ENST00000394468.7	TSL:2 MANE Select	c.1070G>T	p.Gly357Val	missense	Exon 5 of 10	ENSP00000377980.2	A8MVW5-1
	HEPACAM2	ENST00000440868.5	TSL:1	c.1034G>T	p.Gly345Val	missense	Exon 4 of 8	ENSP00000389592.1	C9JN07
	HEPACAM2	ENST00000341723.8	TSL:1	c.1034G>T	p.Gly345Val	missense	Exon 4 of 9	ENSP00000340532.4	A8MVW5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247498 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1444120 Hom.: 0 Cov.: 28 AF XY: 0.00000278 AC XY: 2 AN XY: 719272

African (AFR) AF: 0.00 AC: 0 AN: 32854

American (AMR) AF: 0.0000229 AC: 1 AN: 43756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25796

East Asian (EAS) AF: 0.00 AC: 0 AN: 39388

South Asian (SAS) AF: 0.00 AC: 0 AN: 85134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00000364 AC: 4 AN: 1098516

Other (OTH) AF: 0.00 AC: 0 AN: 59732

GnomAD4 genome Cov.: 32

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	0.16
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	21
DANN	Benign	0.36
DEOGEN2	Benign	0.0064	T
Eigen	Benign	0.011
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.24
Sift	Benign	0.98	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.27	B
Vest4		0.90
MutPred		0.57		Loss of disorder (P = 0.0675)
MVP		0.58
MPC		0.61
ClinPred		0.73	D
GERP RS		5.3
Varity_R		0.35
gMVP		0.86
Mutation Taster		=53/47	polymorphism

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: rs746063573; hg19: chr7-92826866;