rs1774961744

Variant names:

• chr6-142753138-T-G
• rs1774961744
• NM_006734.4:c.7310A>C

Variant summary

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

The NM_006734.4(HIVEP2):​c.7310A>C​(p.Asp2437Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HIVEP2 NM_006734.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.24
• Publications: 0 publications found

Genes affected

HIVEP2 (HGNC:4921): (HIVEP zinc finger 2) This gene encodes a member of a family of closely related, large, zinc finger-containing transcription factors. The encoded protein regulates transcription by binding to regulatory regions of various cellular and viral genes that maybe involved in growth, development and metastasis. The protein contains the ZAS domain comprised of two widely separated regions of zinc finger motifs, a stretch of highly acidic amino acids and a serine/threonine-rich sequence. [provided by RefSeq, Nov 2012]

HIVEP2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 43

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000233138 (HGNC:):

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=0.09483725).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006734.4. 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
	HIVEP2	NM_006734.4	MANE Select	c.7310A>C	p.Asp2437Ala	missense	Exon 10 of 10	NP_006725.3
	HIVEP2	NM_001438449.1		c.7310A>C	p.Asp2437Ala	missense	Exon 10 of 10	NP_001425378.1
	HIVEP2	NM_001438450.1		c.7310A>C	p.Asp2437Ala	missense	Exon 11 of 11	NP_001425379.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIVEP2	ENST00000367603.8	TSL:1 MANE Select	c.7310A>C	p.Asp2437Ala	missense	Exon 10 of 10	ENSP00000356575.2	P31629
	HIVEP2	ENST00000012134.7	TSL:5	c.7310A>C	p.Asp2437Ala	missense	Exon 9 of 9	ENSP00000012134.2	P31629
	HIVEP2	ENST00000367604.6	TSL:5	c.7310A>C	p.Asp2437Ala	missense	Exon 10 of 10	ENSP00000356576.1	P31629

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Intellectual disability, autosomal dominant 43 (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.089
Eigen_PC	Benign	0.017
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.078
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.033	D
Polyphen		0.020	B
Vest4		0.18
MutPred		0.15		Loss of solvent accessibility (P = 0.0249)
MVP		0.068
MPC		0.23
ClinPred		0.28	T
GERP RS		6.0
Varity_R		0.10
gMVP		0.058
Mutation Taster		=87/13	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: rs1774961744; hg19: chr6-143074275;