chr7-93197523-C-G

Variant names:

• chr7-93197523-C-G
• rs200059437
• NM_001039372.4:c.1100G>C

Variant summary

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

The NM_001039372.4(HEPACAM2):​c.1100G>C​(p.Cys367Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C367Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HEPACAM2 NM_001039372.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.546
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13648373).

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.1100G>C	p.Cys367Ser	missense	Exon 5 of 10	NP_001034461.1	A8MVW5-1
	HEPACAM2	NM_001288804.3		c.1169G>C	p.Cys390Ser	missense	Exon 6 of 11	NP_001275733.1	A8MVW5-3
	HEPACAM2	NM_001288810.3		c.1064G>C	p.Cys355Ser	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.1100G>C	p.Cys367Ser	missense	Exon 5 of 10	ENSP00000377980.2	A8MVW5-1
	HEPACAM2	ENST00000440868.5	TSL:1	c.1064G>C	p.Cys355Ser	missense	Exon 4 of 8	ENSP00000389592.1	C9JN07
	HEPACAM2	ENST00000341723.8	TSL:1	c.1064G>C	p.Cys355Ser	missense	Exon 4 of 9	ENSP00000340532.4	A8MVW5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443034 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 718764

⚠️ 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: 32722

American (AMR) AF: 0.0000232 AC: 1 AN: 43172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25732

East Asian (EAS) AF: 0.00 AC: 0 AN: 39376

South Asian (SAS) AF: 0.00 AC: 0 AN: 84834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098666

Other (OTH) AF: 0.00 AC: 0 AN: 59622

⚠️ 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

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	0.096
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.87
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.49	N
PhyloP100		0.55
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.12
Sift	Benign	0.18	T
Sift4G	Benign	0.19	T
Polyphen		0.0050	B
Vest4		0.27
MutPred		0.51		Loss of sheet (P = 0.0054)
MVP		0.32
MPC		0.14
ClinPred		0.13	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.42
Mutation Taster		=91/9	polymorphism

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: rs200059437; hg19: chr7-92826836;