NM_021973.3:c.*1039G>A

Variant names:

• chr4-173526238-C-T
• rs2119788
• NM_021973.3:c.*1039G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021973.3(HAND2):​c.*1039G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,010 control chromosomes in the GnomAD database, including 20,633 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (20628 hom., cov: 32)
  • Exomes 𝑓: 0.50 (5 hom.)
• Consequence: HAND2 NM_021973.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 8 publications found

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-AS1 (HGNC:48872): (HAND2 antisense RNA 1) Predicted to be involved in positive regulation of gene expression. Predicted to act upstream of or within with a positive effect on cardiac right ventricle morphogenesis. Predicted to act upstream of or within transcription elongation from RNA polymerase II promoter. Predicted to be located in chromatin; cytoplasm; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000302337 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021973.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAND2	NM_021973.3	MANE Select	c.*1039G>A		3_prime_UTR	Exon 2 of 2	NP_068808.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAND2	ENST00000359562.4	TSL:1 MANE Select	c.*1039G>A		3_prime_UTR	Exon 2 of 2	ENSP00000352565.4
	HAND2	ENST00000503024.1	TSL:3	n.*264+775G>A		intron	N/A	ENSP00000427084.1
	HAND2-AS1	ENST00000785257.1		n.64+4809C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.514 AC: 77987 AN: 151868 Hom.: 20581 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.500 AC: 12 AN: 24 Hom.: 5 Cov.: 0 AF XY: 0.625 AC XY: 10 AN XY: 16

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.688 AC: 11 AN: 16

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.514 AC: 78089 AN: 151986 Hom.: 20628 Cov.: 32 AF XY: 0.518 AC XY: 38445 AN XY: 74278

African (AFR) AF: 0.629 AC: 26074 AN: 41438

American (AMR) AF: 0.503 AC: 7679 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1753 AN: 3472

East Asian (EAS) AF: 0.380 AC: 1960 AN: 5154

South Asian (SAS) AF: 0.442 AC: 2130 AN: 4818

European-Finnish (FIN) AF: 0.574 AC: 6051 AN: 10550

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30958 AN: 67962

Other (OTH) AF: 0.481 AC: 1014 AN: 2108

Alfa AF: 0.467 Hom.: 38123

Bravo AF: 0.514

Asia WGS AF: 0.454 AC: 1580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.48
PhyloP100		0.058
Mutation Taster		=100/0	polymorphism (auto)

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: rs2119788; hg19: chr4-174447389;