4-173526238-C-T

Position:

• chr4-173526238-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAND2	NM_021973.3	c.*1039G>A		3_prime_UTR_variant	2/2	ENST00000359562.4	NP_068808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAND2	ENST00000359562	c.*1039G>A		3_prime_UTR_variant	2/2	1	NM_021973.3	ENSP00000352565.4
HAND2	ENST00000503024.1	n.*264+775G>A		intron_variant		3		ENSP00000427084.1

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

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.688

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.481

Alfa AF: 0.456 Hom.: 25755

Bravo AF: 0.514

Asia WGS AF: 0.454 AC: 1580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs2119788; hg19: chr4-174447389;