chr1-109619568-C-T

Variant names:

• chr1-109619568-C-T
• rs56079255
• NM_001377295.2:c.-139G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001379232.1(GNAT2):​c.-54+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 152,548 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (105 hom., cov: 33)
  • Exomes 𝑓: 0.012 (0 hom.)
• Consequence: GNAT2 NM_001379232.1 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.925
• Publications: 2 publications found

Genes affected

GNAT2 (HGNC:4394): (G protein subunit alpha transducin 2) Transducin is a 3-subunit guanine nucleotide-binding protein (G protein) which stimulates the coupling of rhodopsin and cGMP-phoshodiesterase during visual impulses. The transducin alpha subunits in rods and cones are encoded by separate genes. This gene encodes the alpha subunit in cones. [provided by RefSeq, Jul 2008]

AMPD2 (HGNC:469): (adenosine monophosphate deaminase 2) The protein encoded by this gene is important in purine metabolism by converting AMP to IMP. The encoded protein, which acts as a homotetramer, is one of three AMP deaminases found in mammals. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

AMPD2 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 9

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• hereditary spastic paraplegia 63

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-109619568-C-T is Benign according to our data. Variant chr1-109619568-C-T is described in ClinVar as Benign. ClinVar VariationId is 1246281.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency = 0.5 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379232.1. 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
	GNAT2	NM_001377295.2	MANE Select	c.-139G>A		5_prime_UTR	Exon 1 of 9	NP_001364224.1	P19087
	GNAT2	NM_001379232.1		c.-54+7G>A		splice_region intron	N/A	NP_001366161.1	Q5T697

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT2	ENST00000679935.1	MANE Select	c.-139G>A		5_prime_UTR	Exon 1 of 9	ENSP00000505083.1	P19087
	GNAT2	ENST00000872462.1		c.-139G>A		5_prime_UTR	Exon 1 of 10	ENSP00000542521.1
	GNAT2	ENST00000872464.1		c.-135G>A		5_prime_UTR	Exon 1 of 9	ENSP00000542523.1

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4656 AN: 152266 Hom.: 105 Cov.: 33

Gnomad AFR AF: 0.00805

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.0316

GnomAD4 exome AF: 0.0122 AC: 2 AN: 164 Hom.: 0 Cov.: 0 AF XY: 0.00862 AC XY: 1 AN XY: 116

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 122

European-Finnish (FIN) AF: 0.0625 AC: 1 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0305 AC: 4655 AN: 152384 Hom.: 105 Cov.: 33 AF XY: 0.0295 AC XY: 2200 AN XY: 74512

African (AFR) AF: 0.00803 AC: 334 AN: 41604

American (AMR) AF: 0.0305 AC: 467 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4830

European-Finnish (FIN) AF: 0.0248 AC: 263 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0503 AC: 3421 AN: 68042

Other (OTH) AF: 0.0313 AC: 66 AN: 2110

Alfa AF: 0.0426 Hom.: 20

Bravo AF: 0.0299

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.78
PhyloP100		-0.93
PromoterAI		-0.017	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56079255; hg19: chr1-110162190;