rs184972478

Variant names:

• chr7-93197551-T-A
• rs184972478
• NM_001039372.4:c.1072A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-93197551-T-A
• chr7-93197551-T-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.1072A>T​(p.Ile358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,597,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: HEPACAM2 NM_001039372.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.943
• 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=0.1261982).

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.1072A>T	p.Ile358Leu	missense	Exon 5 of 10	NP_001034461.1	A8MVW5-1
	HEPACAM2	NM_001288804.3		c.1141A>T	p.Ile381Leu	missense	Exon 6 of 11	NP_001275733.1	A8MVW5-3
	HEPACAM2	NM_001288810.3		c.1036A>T	p.Ile346Leu	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.1072A>T	p.Ile358Leu	missense	Exon 5 of 10	ENSP00000377980.2	A8MVW5-1
	HEPACAM2	ENST00000440868.5	TSL:1	c.1036A>T	p.Ile346Leu	missense	Exon 4 of 8	ENSP00000389592.1	C9JN07
	HEPACAM2	ENST00000341723.8	TSL:1	c.1036A>T	p.Ile346Leu	missense	Exon 4 of 9	ENSP00000340532.4	A8MVW5-2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152070 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000564 AC: 14 AN: 248302 AF XY: 0.0000670

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000888

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000710

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000284 AC: 41 AN: 1444856 Hom.: 0 Cov.: 28 AF XY: 0.0000361 AC XY: 26 AN XY: 719680

African (AFR) AF: 0.00 AC: 0 AN: 32900

American (AMR) AF: 0.0000682 AC: 3 AN: 43958

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25836

East Asian (EAS) AF: 0.00 AC: 0 AN: 39416

South Asian (SAS) AF: 0.0000351 AC: 3 AN: 85392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5716

European-Non Finnish (NFE) AF: 0.0000264 AC: 29 AN: 1098582

Other (OTH) AF: 0.0000669 AC: 4 AN: 59804

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74392

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000495 AC: 6

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	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.94
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.069
Sift	Benign	0.044	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.070	B
Vest4		0.43
MutPred		0.40		Gain of catalytic residue at I358 (P = 0.0573)
MVP		0.17
MPC		0.11
ClinPred		0.076	T
GERP RS		1.6
Varity_R		0.078
gMVP		0.66
Mutation Taster		=90/10	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: rs184972478; hg19: chr7-92826864;