2-36981780-C-T

Variant names:

• chr2-36981780-C-T
• NM_019024.3:c.5926G>A

Variant summary

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

The NM_019024.3(HEATR5B):​c.5926G>A​(p.Ala1976Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HEATR5B NM_019024.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.66
• Publications: 0 publications found

Genes affected

HEATR5B (HGNC:29273): (HEAT repeat containing 5B) Predicted to be involved in endocytosis; protein localization; and retrograde transport, endosome to Golgi. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

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_019024.3. 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
	HEATR5B	NM_019024.3	MANE Select	c.5926G>A	p.Ala1976Thr	missense	Exon 36 of 36	NP_061897.1	Q9P2D3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR5B	ENST00000233099.6	TSL:1 MANE Select	c.5926G>A	p.Ala1976Thr	missense	Exon 36 of 36	ENSP00000233099.5	Q9P2D3-1
	HEATR5B	ENST00000903982.1		c.5926G>A	p.Ala1976Thr	missense	Exon 36 of 36	ENSP00000574041.1
	HEATR5B	ENST00000920714.1		c.5926G>A	p.Ala1976Thr	missense	Exon 36 of 36	ENSP00000590773.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Uncertain	0.44
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.7
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.14
Sift	Benign	0.55	T
Sift4G	Benign	0.53	T
Polyphen		0.081	B
Vest4		0.77
MutPred		0.68		Loss of stability (P = 0.0707)
MVP		0.56
MPC		0.13
ClinPred		0.69	D
GERP RS		5.6
Varity_R		0.15
gMVP		0.48
Mutation Taster		=62/38	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

hg19: chr2-37208923;