Variant 4-173527281-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021973.3(HAND2):c.650A>C(p.Gln217Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000962 in 1,610,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

HAND2
NM_021973.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.91

Variant links:

Genes affected

HAND2 (HGNC:4808): (heart and neural crest derivatives expressed 2) The protein encoded by this gene belongs to the basic helix-loop-helix family of transcription factors. This gene product is one of two closely related family members, the HAND proteins, which are asymmetrically expressed in the developing ventricular chambers and play an essential role in cardiac morphogenesis. Working in a complementary fashion, they function in the formation of the right ventricle and aortic arch arteries, implicating them as mediators of congenital heart disease. In addition, this transcription factor plays an important role in limb and branchial arch development. [provided by RefSeq, Jul 2008]

HAND2 links:

HAND2-AS1 (HGNC:):

HAND2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02276957).

BP6

Variant 4-173527281-T-G is Benign according to our data. Variant chr4-173527281-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2703085.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 91 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAND2	NM_021973.3 linkuse as main transcript	c.650A>C	p.Gln217Pro	missense_variant	2/2	ENST00000359562.4	NP_068808.1	P61296-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HAND2	ENST00000359562.4 linkuse as main transcript	c.650A>C	p.Gln217Pro	missense_variant	2/2	1	NM_021973.3	ENSP00000352565.4	P61296-1
HAND2	ENST00000503024.1 linkuse as main transcript	n.272A>C		non_coding_transcript_exon_variant	2/4	3		ENSP00000427084.1	H0YAH1
HAND2-AS1	ENST00000512099.5 linkuse as main transcript	n.12T>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000153

AC:

AN:

248832

Hom.:

AF XY:

0.0000964

AC XY:

AN XY:

134820

show subpopulations

Gnomad AFR exome

AF:

0.00235

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000439

AC:

AN:

1458262

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

725722

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000598

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000382

Hom.:

Bravo

AF:

0.000691

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000189

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.0015

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;D

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.023

T;T

MetaSVM

Pathogenic

1.1

MutationAssessor

Benign

0.76

N;.

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.6

N;.

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.35

MVP

0.92

MPC

2.2

ClinPred

0.14

GERP RS

5.8

Varity_R

0.69

gMVP

0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over