rs1352896143

Variant names:

• chr2-176107660-G-A
• rs1352896143
• NM_021192.3:c.305G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-176107660-G-A
• chr2-176107660-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_021192.3(HOXD11):​c.305G>A​(p.Gly102Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 978,846 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00065 (3 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: HOXD11 NM_021192.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

Genes affected

HOXD11 (HGNC:5134): (homeobox D11) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. The product of the mouse Hoxd11 gene plays a role in forelimb morphogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03783506).
• BS2: High AC in GnomAd4 at 94 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021192.3. 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
	HOXD11	NM_021192.3	MANE Select	c.305G>A	p.Gly102Asp	missense	Exon 1 of 2	NP_067015.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXD11	ENST00000249504.7	TSL:3 MANE Select	c.305G>A	p.Gly102Asp	missense	Exon 1 of 2	ENSP00000249504.5	P31277
	HOXD11	ENST00000498438.1	TSL:1	n.412-1247G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000646 AC: 94 AN: 145584 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00633

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: 0.0000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000108 AC: 9 AN: 833262 Hom.: 0 Cov.: 22 AF XY: 0.0000104 AC XY: 4 AN XY: 385744

African (AFR) AF: 0.0000637 AC: 1 AN: 15710

American (AMR) AF: 0.00350 AC: 4 AN: 1142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5208

East Asian (EAS) AF: 0.00 AC: 0 AN: 3776

South Asian (SAS) AF: 0.00 AC: 0 AN: 17220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1638

European-Non Finnish (NFE) AF: 0.00000395 AC: 3 AN: 760198

Other (OTH) AF: 0.0000365 AC: 1 AN: 27396

GnomAD4 genome AF: 0.000646 AC: 94 AN: 145584 Hom.: 3 Cov.: 32 AF XY: 0.00100 AC XY: 71 AN XY: 70742

African (AFR) AF: 0.00 AC: 0 AN: 40646

American (AMR) AF: 0.00633 AC: 93 AN: 14686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3386

East Asian (EAS) AF: 0.00 AC: 0 AN: 4996

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65620

Other (OTH) AF: 0.00 AC: 0 AN: 2008

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000620

ClinVar

ClinVar submissions as Germline

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	0.48
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.33	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.3
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.15
Sift	Benign	0.41	T
Sift4G	Uncertain	0.011	D
Polyphen		0.016	B
Vest4		0.20
MutPred		0.18		Gain of phosphorylation at Y103 (P = 0.0966)
MVP		0.84
ClinPred		0.078	T
GERP RS		2.1
PromoterAI		0.086	Neutral
Varity_R		0.10
gMVP		0.57
Mutation Taster		=88/12	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: rs1352896143; hg19: chr2-176972388;